Skip to main content
Top
Published in: Rheumatology International 11/2018

01-11-2018 | Review

Regulation of energy metabolism in the growth plate and osteoarthritic chondrocytes

Authors: Elena V. Tchetina, Galina A. Markova

Published in: Rheumatology International | Issue 11/2018

Login to get access

Abstract

Osteoarthritis (OA) is a chronic disorder associated mainly with pain, limited range of motion, stiffness, low-grade systemic inflammation, and articular cartilage destruction. Recent studies have demonstrated the involvement of chondrocyte differentiation (hypertrophy) as one of the mechanisms in cartilage degradation in OA. This implicates the involvement of principal changes in the regulation of cellular function associated with profound alterations in chondrocyte energy metabolism in the course of cartilage resorption. Therefore, this review describes the major energy-generating pathways and their regulatory molecules used by the growth plate chondrocytes during endochondral ossification and by articular chondrocytes in OA. These regulatory molecules facilitate either the glycolytic pathway of energy generation, which controls cell proliferation, or mitochondrial oxidative phosphorylation promoted by AMPK and sirtuins and responsible for tissue regeneration. Consideration of the disturbances in energy metabolic pathways associated with OA might provide an approach to disclose the primary causes of the disease’s development and progression. Medline/PubMed was searched for publications in English using key words: osteoarthritis, epiphyseal growth plate, articular cartilage, glycolysis, oxidative phosphorylation, and regulation of energy metabolism.
Literature
1.
go back to reference Poole AR, Guilak F, Abramson SB (2007) Etiopathogenesis of osteoarthritis. In: Moskowitz RW, Altman RD, Hochberg MC, Buckwalter JA, Goldberg VM (eds) Osteoarthritis: diagnosis and medical/surgical management, 4th edn. Williams & Wilkins, Philadelphia, pp 27–49 Poole AR, Guilak F, Abramson SB (2007) Etiopathogenesis of osteoarthritis. In: Moskowitz RW, Altman RD, Hochberg MC, Buckwalter JA, Goldberg VM (eds) Osteoarthritis: diagnosis and medical/surgical management, 4th edn. Williams & Wilkins, Philadelphia, pp 27–49
2.
go back to reference Little CB, Fosang AJ (2010) Is cartilage matrix breakdown an appropriate therapeutic target in osteoarthritis–insights from studies of aggrecan and collagen proteolysis? Curr Drug Targets 11:561–575PubMed Little CB, Fosang AJ (2010) Is cartilage matrix breakdown an appropriate therapeutic target in osteoarthritis–insights from studies of aggrecan and collagen proteolysis? Curr Drug Targets 11:561–575PubMed
3.
go back to reference Bondeson J (2011) Are we moving in the right direction with osteoarthritis drug discovery? Expert Opin Ther Targets 15:1355–1368PubMed Bondeson J (2011) Are we moving in the right direction with osteoarthritis drug discovery? Expert Opin Ther Targets 15:1355–1368PubMed
4.
go back to reference Berenbaum F (2013) Osteoarthritis as an inflammatory disease (osteoarthritis is not osteoarthrosis!). Osteoarthr Cartil 21:16–21 Berenbaum F (2013) Osteoarthritis as an inflammatory disease (osteoarthritis is not osteoarthrosis!). Osteoarthr Cartil 21:16–21
5.
go back to reference Berenbaum F, Timothy M, Griffin, Ru Liu-Bryan (2017) Metabolic regulation of inflammation in osteoarthritis. Arthritis Rheumatol 69:9–21PubMedPubMedCentral Berenbaum F, Timothy M, Griffin, Ru Liu-Bryan (2017) Metabolic regulation of inflammation in osteoarthritis. Arthritis Rheumatol 69:9–21PubMedPubMedCentral
6.
go back to reference Yagi R, McBurney D, Laverty D, Weiner S, Horton WEJr (2005) Intrajoint comparison of gene expression patterns in human osteoarthritis suggest a change in chondrocyte phenotype. J Orthop Res 23:1128–1138PubMed Yagi R, McBurney D, Laverty D, Weiner S, Horton WEJr (2005) Intrajoint comparison of gene expression patterns in human osteoarthritis suggest a change in chondrocyte phenotype. J Orthop Res 23:1128–1138PubMed
7.
go back to reference Kirsch T, Swoboda B, Nah H (2000) Activation of annexin II and V expression, terminal differentiation, mineralization and apoptosis in human osteoarthritic cartilage. Osteoarthr Cartil 8:294–302 Kirsch T, Swoboda B, Nah H (2000) Activation of annexin II and V expression, terminal differentiation, mineralization and apoptosis in human osteoarthritic cartilage. Osteoarthr Cartil 8:294–302
8.
go back to reference Pullig O, Weseloh G, Ronneberger D, Käkönen S, Swoboda B (2000) Chondrocyte differentiation in human osteoarthritis: expression of osteocalcin in normal and osteoarthritic cartilage and bone. Calcif Tissue Int 67:230–240PubMed Pullig O, Weseloh G, Ronneberger D, Käkönen S, Swoboda B (2000) Chondrocyte differentiation in human osteoarthritis: expression of osteocalcin in normal and osteoarthritic cartilage and bone. Calcif Tissue Int 67:230–240PubMed
9.
go back to reference Johnson K, Terkeltaub R (2004) Upregulated ank expression in osteoarthritis can promote both chondrocyte MMP-13 expression and calcification via chondrocyte extracellular PPi excess. Osteoarthr Cartil 12:321–335 Johnson K, Terkeltaub R (2004) Upregulated ank expression in osteoarthritis can promote both chondrocyte MMP-13 expression and calcification via chondrocyte extracellular PPi excess. Osteoarthr Cartil 12:321–335
10.
go back to reference Robertson CM, Pennock AT, Harwood FL, Pomerleau AC, Allen RT, Amiel D (2006) Characterization of pro-apoptotic and matrix-degradative gene expression following induction of osteoarthritis in mature and aged rabbits. Osteoarthr Cartil 14:471–476 Robertson CM, Pennock AT, Harwood FL, Pomerleau AC, Allen RT, Amiel D (2006) Characterization of pro-apoptotic and matrix-degradative gene expression following induction of osteoarthritis in mature and aged rabbits. Osteoarthr Cartil 14:471–476
11.
go back to reference Tchetina EV, Squires G, Poole AR (2005) Increased type II collagen degradation and very early focal cartilage degeneration is associated with upregulation of chondrocyte differentiation related genes in early human articular cartilage lesions. J Rheumatol 32:876–886PubMed Tchetina EV, Squires G, Poole AR (2005) Increased type II collagen degradation and very early focal cartilage degeneration is associated with upregulation of chondrocyte differentiation related genes in early human articular cartilage lesions. J Rheumatol 32:876–886PubMed
12.
go back to reference Zhang X, Crawford R, Xiao Y (2016) Inhibition of vascular endothelial growth factor with shRNA in chondrocytes ameliorates osteoarthritis. J Mol Med (Berl) 94:787–798 Zhang X, Crawford R, Xiao Y (2016) Inhibition of vascular endothelial growth factor with shRNA in chondrocytes ameliorates osteoarthritis. J Mol Med (Berl) 94:787–798
13.
go back to reference Xu W, Xie Y, Wang Q, Wang X, Luo F, Zhou S, Wang Z, Huang J, Tan Q, Jin M, Qi H, Tang J, Chen L, Du X, Zhao C, Liang G, Chen L (2016) A novel fibroblast growth factor receptor 1 inhibitor protects against cartilage degradation in a murine model of osteoarthritis. Sci Rep 6:24042PubMedPubMedCentral Xu W, Xie Y, Wang Q, Wang X, Luo F, Zhou S, Wang Z, Huang J, Tan Q, Jin M, Qi H, Tang J, Chen L, Du X, Zhao C, Liang G, Chen L (2016) A novel fibroblast growth factor receptor 1 inhibitor protects against cartilage degradation in a murine model of osteoarthritis. Sci Rep 6:24042PubMedPubMedCentral
14.
go back to reference Chen S, Fu P, Cong R, Wu H, Pei M (2015) Strategies to minimize hypertrophy in cartilage engineering and regeneration. Genes Dis 2:76–95PubMedPubMedCentral Chen S, Fu P, Cong R, Wu H, Pei M (2015) Strategies to minimize hypertrophy in cartilage engineering and regeneration. Genes Dis 2:76–95PubMedPubMedCentral
15.
go back to reference Agathocleous M, Harris WA (2013) Metabolism in physiological cell proliferation and differentiation. Trends Cell Biol 23:484–492PubMed Agathocleous M, Harris WA (2013) Metabolism in physiological cell proliferation and differentiation. Trends Cell Biol 23:484–492PubMed
16.
go back to reference Agathocleous M, Love NK, Randlett O, Harris JJ, Liu J, Murray AJ, Harris WA (2012) Metabolic differentiation in the embryonic retina. Nat Cell Biol 14:859–864PubMedPubMedCentral Agathocleous M, Love NK, Randlett O, Harris JJ, Liu J, Murray AJ, Harris WA (2012) Metabolic differentiation in the embryonic retina. Nat Cell Biol 14:859–864PubMedPubMedCentral
17.
go back to reference Vander Heiden MG, Cantley LC, Thompson CB (2009) Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 324:1029–1033PubMedPubMedCentral Vander Heiden MG, Cantley LC, Thompson CB (2009) Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 324:1029–1033PubMedPubMedCentral
18.
go back to reference Komen JC, Thorburn DR (2014) Turn up the power–pharmacological activation of mitochondrial biogenesis in mouse models. Br J Pharmacol 171(8):1818–1836PubMedPubMedCentral Komen JC, Thorburn DR (2014) Turn up the power–pharmacological activation of mitochondrial biogenesis in mouse models. Br J Pharmacol 171(8):1818–1836PubMedPubMedCentral
19.
go back to reference Wilson DF (2013) Regulation of cellular metabolism: programming and maintaining metabolic homeostasis. J Appl Physiol (1985) 11 5:1583–1588 Wilson DF (2013) Regulation of cellular metabolism: programming and maintaining metabolic homeostasis. J Appl Physiol (1985) 11 5:1583–1588
20.
go back to reference Zoncu R, Efeyan A, Sabatini DM (2011) mTOR. From growth signal integration to cancer, diabetes and ageing. Nat Rev Mol Cell Biol 12:21–35PubMed Zoncu R, Efeyan A, Sabatini DM (2011) mTOR. From growth signal integration to cancer, diabetes and ageing. Nat Rev Mol Cell Biol 12:21–35PubMed
21.
go back to reference Martin TD, Chen XW, Kaplan RE, Saltiel AR, Walker CL, Reiner DJ, Der CJ (2014) Ral and Rheb GTPase activating proteins integrate mTOR and GTPase signaling in aging, autophagy, and tumor cell invasion. Mol Cell 53:209–220PubMedPubMedCentral Martin TD, Chen XW, Kaplan RE, Saltiel AR, Walker CL, Reiner DJ, Der CJ (2014) Ral and Rheb GTPase activating proteins integrate mTOR and GTPase signaling in aging, autophagy, and tumor cell invasion. Mol Cell 53:209–220PubMedPubMedCentral
22.
go back to reference Marshall S (2006) Role of insulin, adipocyte hormones, and nutrient-sensing pathways in regulating fuel metabolism and energy homeostasis: a nutritional perspective of diabetes, obesity, and cancer. Sci STKE 2006:re7PubMed Marshall S (2006) Role of insulin, adipocyte hormones, and nutrient-sensing pathways in regulating fuel metabolism and energy homeostasis: a nutritional perspective of diabetes, obesity, and cancer. Sci STKE 2006:re7PubMed
23.
go back to reference Wang RH, Kim HS, Xiao C, Xu X, Gavrilova O, Deng CX (2011) Hepatic Sirt1 deficiency in mice impairs mTorc2/Akt signaling and results in hyperglycemia, oxidative damage, and insulin resistance. J Clin Investig 121:4477–4490PubMedPubMedCentral Wang RH, Kim HS, Xiao C, Xu X, Gavrilova O, Deng CX (2011) Hepatic Sirt1 deficiency in mice impairs mTorc2/Akt signaling and results in hyperglycemia, oxidative damage, and insulin resistance. J Clin Investig 121:4477–4490PubMedPubMedCentral
24.
go back to reference Vanhaesebroeck B, Waterfield MD (1999) Signaling by distinct classes of phosphoinositide 3-kinases. Exp Cell Res 253:239–254PubMed Vanhaesebroeck B, Waterfield MD (1999) Signaling by distinct classes of phosphoinositide 3-kinases. Exp Cell Res 253:239–254PubMed
25.
go back to reference Di Magno L, Manzi D, D’Amico D, Coni S, Macone A, Infante P, Di Marcotullio L, De Smaele E, Ferretti E, Screpanti I, Agostinelli E, Gulino A, Canettieri G (2014) Druggable glycolytic requirement for Hedgehog-dependent neuronal and medulloblastoma growth. Cell Cycle 13:3404–3413PubMedPubMedCentral Di Magno L, Manzi D, D’Amico D, Coni S, Macone A, Infante P, Di Marcotullio L, De Smaele E, Ferretti E, Screpanti I, Agostinelli E, Gulino A, Canettieri G (2014) Druggable glycolytic requirement for Hedgehog-dependent neuronal and medulloblastoma growth. Cell Cycle 13:3404–3413PubMedPubMedCentral
26.
go back to reference Gonnissen A, Isebaert S, Haustermans K (2015) Targeting the Hedgehog signaling pathway in cancer: beyond Smoothened. Oncotarget 6:13899–13913PubMedPubMedCentral Gonnissen A, Isebaert S, Haustermans K (2015) Targeting the Hedgehog signaling pathway in cancer: beyond Smoothened. Oncotarget 6:13899–13913PubMedPubMedCentral
28.
go back to reference Kim JW, Tchernyshyov I, Semenza GL, Dang CV (2006) HIF-1-mediated expression of pyruvate dehydrogenase kinase: a metabolic switch required for cellular adaptation to hypoxia. Cell Metab 3:177–185PubMed Kim JW, Tchernyshyov I, Semenza GL, Dang CV (2006) HIF-1-mediated expression of pyruvate dehydrogenase kinase: a metabolic switch required for cellular adaptation to hypoxia. Cell Metab 3:177–185PubMed
29.
go back to reference Zhang H, Bosch-Marce M, Shimoda LA, Tan YS, Baek JH, Wesley JB, Gonzalez FJ, Semenza GL (2008) Mitochondrial autophagy is an HIF-1-dependent adaptive metabolic response to hypoxia. J Biol Chem 283:10892–10903PubMedPubMedCentral Zhang H, Bosch-Marce M, Shimoda LA, Tan YS, Baek JH, Wesley JB, Gonzalez FJ, Semenza GL (2008) Mitochondrial autophagy is an HIF-1-dependent adaptive metabolic response to hypoxia. J Biol Chem 283:10892–10903PubMedPubMedCentral
30.
go back to reference Liu Y, Ma Z, Zhao C, Wang Y, Wu G, Xiao J, McClain CJ, Li X, Feng W (2014) HIF-1α and HIF-2α are critically involved in hypoxia-induced lipid accumulation in hepatocytes through reducing PGC-1α-mediated fatty acid β-oxidation. Toxicol Lett 226:117–123PubMed Liu Y, Ma Z, Zhao C, Wang Y, Wu G, Xiao J, McClain CJ, Li X, Feng W (2014) HIF-1α and HIF-2α are critically involved in hypoxia-induced lipid accumulation in hepatocytes through reducing PGC-1α-mediated fatty acid β-oxidation. Toxicol Lett 226:117–123PubMed
31.
go back to reference Chandel NS, McClintock DS, Feliciano CE, Wood TM, Melendez JA, Rodriguez AM, Schumacker PT (2000) Reactive oxygen species generated at mitochondrial complex III stabilize hypoxia-inducible factor-1alpha during hypoxia: a mechanism of O2 sensing. J Biol Chem 275:25130–25138PubMed Chandel NS, McClintock DS, Feliciano CE, Wood TM, Melendez JA, Rodriguez AM, Schumacker PT (2000) Reactive oxygen species generated at mitochondrial complex III stabilize hypoxia-inducible factor-1alpha during hypoxia: a mechanism of O2 sensing. J Biol Chem 275:25130–25138PubMed
32.
go back to reference Tello D, Balsa E, Acosta-Iborra B, Fuertes-Yebra E, Elorza A, Ordonez A, Corral-Escariz M, Soro I, López-Bernardo E, Perales-Clemente E, Martínez-Ruiz A, Enríquez JA, Aragonés J, Cadenas S, Landázuri MO (2011) Induction of the mitochondrial NDUFA4L2 protein by HIF-1alpha decreases oxygen consumption by inhibiting Complex I activity. Cell Metab 14:768–779PubMed Tello D, Balsa E, Acosta-Iborra B, Fuertes-Yebra E, Elorza A, Ordonez A, Corral-Escariz M, Soro I, López-Bernardo E, Perales-Clemente E, Martínez-Ruiz A, Enríquez JA, Aragonés J, Cadenas S, Landázuri MO (2011) Induction of the mitochondrial NDUFA4L2 protein by HIF-1alpha decreases oxygen consumption by inhibiting Complex I activity. Cell Metab 14:768–779PubMed
33.
go back to reference Fukuda R, Zhang H, Kim JW, Shimoda L, Dang CV, Semenza GL (2007) HIF-1 regulates cytochrome oxidase subunits to optimize efficiency of respiration in hypoxic cells. Cell 129:111–122PubMed Fukuda R, Zhang H, Kim JW, Shimoda L, Dang CV, Semenza GL (2007) HIF-1 regulates cytochrome oxidase subunits to optimize efficiency of respiration in hypoxic cells. Cell 129:111–122PubMed
34.
go back to reference Conacci-Sorrell M, McFerrin L, Eisenman RN (2014) An overview of MYC and its interactome. Cold Spring Harb Perspect Med 4:a014357.5 Conacci-Sorrell M, McFerrin L, Eisenman RN (2014) An overview of MYC and its interactome. Cold Spring Harb Perspect Med 4:a014357.5
35.
go back to reference Shim H, Dolde C, Lewis BC, Wu CS, Dang G, Jungmann RA, Dalla-Favera R, Dang CV (1997) c-Myc transactivation of LDH-A: implications for tumor metabolism and growth. Proc Natl Acad Sci USA 94:6658–6663PubMedPubMedCentral Shim H, Dolde C, Lewis BC, Wu CS, Dang G, Jungmann RA, Dalla-Favera R, Dang CV (1997) c-Myc transactivation of LDH-A: implications for tumor metabolism and growth. Proc Natl Acad Sci USA 94:6658–6663PubMedPubMedCentral
36.
go back to reference Zhou ZQ, Shung CY, Ota S, Akiyama H, Keene DR, Hurlin PJ (2011) Sequential and coordinated actions of c-Myc and N-Myc control appendicular skeletal development. PLoS One 6:e18795PubMedPubMedCentral Zhou ZQ, Shung CY, Ota S, Akiyama H, Keene DR, Hurlin PJ (2011) Sequential and coordinated actions of c-Myc and N-Myc control appendicular skeletal development. PLoS One 6:e18795PubMedPubMedCentral
37.
go back to reference Gwinn DM, Shackelford DB, Egan DF, Mihaylova MM, Mery A, Vasquez DS, Turk BE, Shaw RJ (2008) AMPK phosphorylation of raptor mediates a metabolic checkpoint. Mol Cell 30:214–226PubMedPubMedCentral Gwinn DM, Shackelford DB, Egan DF, Mihaylova MM, Mery A, Vasquez DS, Turk BE, Shaw RJ (2008) AMPK phosphorylation of raptor mediates a metabolic checkpoint. Mol Cell 30:214–226PubMedPubMedCentral
38.
go back to reference June RK, Liu-Bryan R, Long F, Griffin TM (2016) Emerging role of metabolic signaling in synovial joint remodeling and osteoarthritis. J Orthop Res 34:2048–2058PubMedPubMedCentral June RK, Liu-Bryan R, Long F, Griffin TM (2016) Emerging role of metabolic signaling in synovial joint remodeling and osteoarthritis. J Orthop Res 34:2048–2058PubMedPubMedCentral
39.
go back to reference Park S, Mori R, Shimokawa I (2013) Do sirtuins promote mammalian longevity? A critical review on its relevance to the longevity effect induced by calorie restriction. Molecules Cells 35:474–480PubMedPubMedCentral Park S, Mori R, Shimokawa I (2013) Do sirtuins promote mammalian longevity? A critical review on its relevance to the longevity effect induced by calorie restriction. Molecules Cells 35:474–480PubMedPubMedCentral
40.
go back to reference Houtkooper RH, Pirinen E, Auwerx J (2012) Sirtuins as regulators of metabolism and healthspan. Nat Rev Mol Cell Biol 13:225–238PubMedPubMedCentral Houtkooper RH, Pirinen E, Auwerx J (2012) Sirtuins as regulators of metabolism and healthspan. Nat Rev Mol Cell Biol 13:225–238PubMedPubMedCentral
41.
go back to reference Salminen A, Kaarniranta K (2012) AMP-activated protein kinase (AMPK) controls the aging process via an integrated signaling network. Ageing Res Rev 11:230–241PubMed Salminen A, Kaarniranta K (2012) AMP-activated protein kinase (AMPK) controls the aging process via an integrated signaling network. Ageing Res Rev 11:230–241PubMed
42.
go back to reference Um JH, Park SJ, Kang H, Yang S, Foretz M, McBurney MW, Kim MK, Viollet B, Chung JH (2010) AMP-activated protein kinase-deficient mice are resistant to the metabolic effects of resveratrol. Diabetes 59:554–563PubMed Um JH, Park SJ, Kang H, Yang S, Foretz M, McBurney MW, Kim MK, Viollet B, Chung JH (2010) AMP-activated protein kinase-deficient mice are resistant to the metabolic effects of resveratrol. Diabetes 59:554–563PubMed
43.
go back to reference Maes C (2017) Signaling pathways effecting crosstalk between cartilage and adjacent tissues: seminars in cell and developmental biology: The biology and pathology of cartilage. Semin Cell Dev Biol 62:16–33PubMed Maes C (2017) Signaling pathways effecting crosstalk between cartilage and adjacent tissues: seminars in cell and developmental biology: The biology and pathology of cartilage. Semin Cell Dev Biol 62:16–33PubMed
44.
go back to reference Stambough JL, Brighton CT, Iannotti JP, Storey BT (1984) Characterization of growth plate mitochondria. J Orthop Res 2:235–246PubMed Stambough JL, Brighton CT, Iannotti JP, Storey BT (1984) Characterization of growth plate mitochondria. J Orthop Res 2:235–246PubMed
45.
go back to reference Shapiro IM, Srinivas V (2007) Metabolic consideration of epiphyseal growth: survival responses in a taxing environment. Bone 40:561–567PubMed Shapiro IM, Srinivas V (2007) Metabolic consideration of epiphyseal growth: survival responses in a taxing environment. Bone 40:561–567PubMed
46.
go back to reference Chen J, Long F (2014) mTORC1 signaling controls mammalian skeletal growth through stimulation of protein synthesis. Development 141:2848–2854PubMedPubMedCentral Chen J, Long F (2014) mTORC1 signaling controls mammalian skeletal growth through stimulation of protein synthesis. Development 141:2848–2854PubMedPubMedCentral
47.
go back to reference Yan B, Zhang Z, Jin D, Cai C, Jia C, Liu W, Wang T, Li S, Zhang H, Huang B, Lai P, Wang H, Liu A, Zeng C, Cai D, Jiang Y, Bai X (2016) mTORC1 regulates PTHrP to coordinate chondrocyte growth, proliferation and differentiation. Nat Commun 7:11151PubMedPubMedCentral Yan B, Zhang Z, Jin D, Cai C, Jia C, Liu W, Wang T, Li S, Zhang H, Huang B, Lai P, Wang H, Liu A, Zeng C, Cai D, Jiang Y, Bai X (2016) mTORC1 regulates PTHrP to coordinate chondrocyte growth, proliferation and differentiation. Nat Commun 7:11151PubMedPubMedCentral
48.
go back to reference Fujita T, Azuma Y, Fukuyama R, Hattori Y, Yoshida C, Koida M, Ogita K, Komori T (2004) Runx2 induces osteoblast and chondrocyte differentiation and enhances their migration by coupling with PI3K-Akt signaling. J Cell Biol 166:85–95PubMedPubMedCentral Fujita T, Azuma Y, Fukuyama R, Hattori Y, Yoshida C, Koida M, Ogita K, Komori T (2004) Runx2 induces osteoblast and chondrocyte differentiation and enhances their migration by coupling with PI3K-Akt signaling. J Cell Biol 166:85–95PubMedPubMedCentral
49.
go back to reference Ford-Hutchinson AF, Ali Z, Lines SE, Hallgrímsson B, Boyd SK, Jirik FR (2007) Inactivation of Pten in osteo-chondroprogenitor cells leads to epiphyseal growth plate abnormalities and skeletal overgrowth. J Bone Miner Res 22:1245–1259PubMed Ford-Hutchinson AF, Ali Z, Lines SE, Hallgrímsson B, Boyd SK, Jirik FR (2007) Inactivation of Pten in osteo-chondroprogenitor cells leads to epiphyseal growth plate abnormalities and skeletal overgrowth. J Bone Miner Res 22:1245–1259PubMed
50.
go back to reference Yang G, Sun Q, Teng Y, Li F, Weng T, Yang X (2008) PTEN deficiency causes dyschondroplasia in mice by enhanced hypoxia-inducible factor 1alpha signaling and endoplasmic reticulum stress. Development 135:3587–3597PubMed Yang G, Sun Q, Teng Y, Li F, Weng T, Yang X (2008) PTEN deficiency causes dyschondroplasia in mice by enhanced hypoxia-inducible factor 1alpha signaling and endoplasmic reticulum stress. Development 135:3587–3597PubMed
52.
go back to reference Rajpurohit R, Koch CJ, Tao Z, Teixeira CM, Shapiro IM (1996) Adaptation of chondrocytes to low oxygen tension: relationship between hypoxia and cellular metabolism. J Cell Physiol 168:424–432PubMed Rajpurohit R, Koch CJ, Tao Z, Teixeira CM, Shapiro IM (1996) Adaptation of chondrocytes to low oxygen tension: relationship between hypoxia and cellular metabolism. J Cell Physiol 168:424–432PubMed
53.
go back to reference Cheng S, Aghajanian P, Pourteymoor S, Alarcon C, Mohan S (2016) Prolyl hydroxylase domain-containing protein 2 (Phd2) regulates chondrocyte differentiation and secondary ossification in mice. Sci Rep 6:35748PubMedPubMedCentral Cheng S, Aghajanian P, Pourteymoor S, Alarcon C, Mohan S (2016) Prolyl hydroxylase domain-containing protein 2 (Phd2) regulates chondrocyte differentiation and secondary ossification in mice. Sci Rep 6:35748PubMedPubMedCentral
54.
go back to reference Schipani E, Ryan HE, Didrickson S, Kobayashi T, Knight M, Johnson RS (2001) Hypoxia in cartilage: HIF-1alpha is essential for chondrocyte growth arrest and survival. Genes Dev 15:2865–2876PubMedPubMedCentral Schipani E, Ryan HE, Didrickson S, Kobayashi T, Knight M, Johnson RS (2001) Hypoxia in cartilage: HIF-1alpha is essential for chondrocyte growth arrest and survival. Genes Dev 15:2865–2876PubMedPubMedCentral
55.
go back to reference Im S, Kim DW (2017) Nkx3.2 induces oxygen concentration-independent and lysosome-dependent degradation of HIF-1α to modulate hypoxic responses in chondrocytes. Cell Signal 36:127–138PubMed Im S, Kim DW (2017) Nkx3.2 induces oxygen concentration-independent and lysosome-dependent degradation of HIF-1α to modulate hypoxic responses in chondrocytes. Cell Signal 36:127–138PubMed
56.
go back to reference Tchetina E, Mwale F, Poole AR (2003) Distinct phases of coordinated early and late gene expression in growth plate chondrocytes in relationship to cell proliferation, matrix assembly, remodeling, and cell differentiation. J Bone Miner Res 18:844–851PubMed Tchetina E, Mwale F, Poole AR (2003) Distinct phases of coordinated early and late gene expression in growth plate chondrocytes in relationship to cell proliferation, matrix assembly, remodeling, and cell differentiation. J Bone Miner Res 18:844–851PubMed
57.
go back to reference Vortkamp A, Lee K, Lanske B, Segre GV, Kronenberg HM, Tabin CJ (1996) Regulation of rate of cartilage differentiation by Indian hedgehog and PTH-related protein. Science 273:613–622PubMed Vortkamp A, Lee K, Lanske B, Segre GV, Kronenberg HM, Tabin CJ (1996) Regulation of rate of cartilage differentiation by Indian hedgehog and PTH-related protein. Science 273:613–622PubMed
58.
go back to reference Phornphutkul C, Wu KY, Auyeung V, Chen Q, Gruppuso PA (2008) mTOR signaling contributes to chondrocyte differentiation. Dev Dyn 237:702–712PubMedPubMedCentral Phornphutkul C, Wu KY, Auyeung V, Chen Q, Gruppuso PA (2008) mTOR signaling contributes to chondrocyte differentiation. Dev Dyn 237:702–712PubMedPubMedCentral
59.
go back to reference Stott NS, Chuong CM (1997) Dual action of sonic hedgehog on chondrocyte hypertrophy: retrovirus mediated ectopic sonic hedgehog expression in limb bud micromass culture induces novel cartilage nodules that are positive for alkaline phosphatase and type X collagen. J Cell Sci 110:2691–2701PubMed Stott NS, Chuong CM (1997) Dual action of sonic hedgehog on chondrocyte hypertrophy: retrovirus mediated ectopic sonic hedgehog expression in limb bud micromass culture induces novel cartilage nodules that are positive for alkaline phosphatase and type X collagen. J Cell Sci 110:2691–2701PubMed
60.
go back to reference Tavella S, Biticchi R, Schito A, Minina E, Di Martino D, Pagano A, Vortkamp A, Horton WA, Cancedda R, Garofalo S (2004) Targeted expression of SHH affects chondrocyte differentiation, growth plate organization, and Sox9 expression. J Bone Miner Res 19:1678–1688PubMed Tavella S, Biticchi R, Schito A, Minina E, Di Martino D, Pagano A, Vortkamp A, Horton WA, Cancedda R, Garofalo S (2004) Targeted expression of SHH affects chondrocyte differentiation, growth plate organization, and Sox9 expression. J Bone Miner Res 19:1678–1688PubMed
61.
go back to reference Aizawa T, Kokubun S, Kawamata T, Tanaka Y, Roach HI (1999) c-Myc protein in the rabbit growth plate. Changes in immunolocalisation with age and possible roles from proliferation to apoptosis. J Bone Jt Surg Br 81:921–925 Aizawa T, Kokubun S, Kawamata T, Tanaka Y, Roach HI (1999) c-Myc protein in the rabbit growth plate. Changes in immunolocalisation with age and possible roles from proliferation to apoptosis. J Bone Jt Surg Br 81:921–925
62.
go back to reference Toury R, Wang Y, Hauchecorne M, Balmain N (1999) c-Myc and Mxi1 immunoreactivities in the calcifying areas of the epiphyseal-plate cartilage matrix of growing rats. Bone 24:555–563PubMed Toury R, Wang Y, Hauchecorne M, Balmain N (1999) c-Myc and Mxi1 immunoreactivities in the calcifying areas of the epiphyseal-plate cartilage matrix of growing rats. Bone 24:555–563PubMed
63.
go back to reference Piedra ME, Delgado MD, Ros MA, Leo´n J (2002) c-Myc overexpression increases cell size and impairs cartilage differentiation during chick limb development. Cell Growth Differ 13:185–193PubMed Piedra ME, Delgado MD, Ros MA, Leo´n J (2002) c-Myc overexpression increases cell size and impairs cartilage differentiation during chick limb development. Cell Growth Differ 13:185–193PubMed
64.
go back to reference Bohensky J, Leshinsky S, Srinivas V, Shapiro IM (1982) Chondrocyte autophagy is stimulated by HIF-1 dependent AMPK activation and mTOR suppression. Pediatr Nephrol 25:633–642 Bohensky J, Leshinsky S, Srinivas V, Shapiro IM (1982) Chondrocyte autophagy is stimulated by HIF-1 dependent AMPK activation and mTOR suppression. Pediatr Nephrol 25:633–642
65.
go back to reference Shapiro IM, Golub EE, Kakuta S, Hazelgrove J, Havery J, Chance B, Frasca P (1982) Initiation of endochondral calcification is related to changes in the redox state of hypertrophic chondrocytes. Science 217:950–952PubMed Shapiro IM, Golub EE, Kakuta S, Hazelgrove J, Havery J, Chance B, Frasca P (1982) Initiation of endochondral calcification is related to changes in the redox state of hypertrophic chondrocytes. Science 217:950–952PubMed
66.
go back to reference Piao J, Tsuji K, Ochi H, Iwata M, Koga D, Okawa A, Morita S, Takeda S, Asou Y (2013) Sirt6 regulates postnatal growth plate differentiation and proliferation via Ihh signaling. Sci Rep 3:3022PubMedPubMedCentral Piao J, Tsuji K, Ochi H, Iwata M, Koga D, Okawa A, Morita S, Takeda S, Asou Y (2013) Sirt6 regulates postnatal growth plate differentiation and proliferation via Ihh signaling. Sci Rep 3:3022PubMedPubMedCentral
67.
go back to reference Cooper KL, Oh S, Sung Y, Dasari RR, Kirschner MW, Tabin CJ (2013) Multiple phases of chondrocyte enlargement underlie differences in skeletal proportions. Nature 495:375–378PubMedPubMedCentral Cooper KL, Oh S, Sung Y, Dasari RR, Kirschner MW, Tabin CJ (2013) Multiple phases of chondrocyte enlargement underlie differences in skeletal proportions. Nature 495:375–378PubMedPubMedCentral
68.
go back to reference Wang F, Zhu Y (2011) Aquaporin-1: a potential membrane channel for facilitating the adaptability of rabbit nucleus pulposus cells to an extracellular matrix environment. J Orthop Sci 16:304–312PubMed Wang F, Zhu Y (2011) Aquaporin-1: a potential membrane channel for facilitating the adaptability of rabbit nucleus pulposus cells to an extracellular matrix environment. J Orthop Sci 16:304–312PubMed
69.
go back to reference Zhang Y, Vasheghani F, Li YH, Blati M, Simeone K, Fahmi H, Lussier B, Roughley P, Lagares D, Pelletier JP, Martel-Pelletier J, Kapoor M (2015) Cartilage-specific deletion of mTOR upregulates autophagy and protects mice from osteoarthritis. Ann Rheum Dis 74:1432–1440PubMed Zhang Y, Vasheghani F, Li YH, Blati M, Simeone K, Fahmi H, Lussier B, Roughley P, Lagares D, Pelletier JP, Martel-Pelletier J, Kapoor M (2015) Cartilage-specific deletion of mTOR upregulates autophagy and protects mice from osteoarthritis. Ann Rheum Dis 74:1432–1440PubMed
70.
go back to reference Pollesello P, de Bernard B, Grandolfo M, Paoletti S, Vittur F, Kvam BJ (1991) Energy state of chondrocytes assessed by 31P-NMR studies of preosseous cartilage. Biochem Biophys Res Commun 180:216–222PubMed Pollesello P, de Bernard B, Grandolfo M, Paoletti S, Vittur F, Kvam BJ (1991) Energy state of chondrocytes assessed by 31P-NMR studies of preosseous cartilage. Biochem Biophys Res Commun 180:216–222PubMed
71.
go back to reference Scott JL, Gabrielides C, Davidson RK, Swingler TE, Clark IM, Wallis GA, Boot-Handford RP, Kirkwood TB, Taylor RW, Young DA (2010) Superoxide dismutase downregulation in osteoarthritis progression and end-stage disease. Ann Rheum Dis 69:1502–1510PubMed Scott JL, Gabrielides C, Davidson RK, Swingler TE, Clark IM, Wallis GA, Boot-Handford RP, Kirkwood TB, Taylor RW, Young DA (2010) Superoxide dismutase downregulation in osteoarthritis progression and end-stage disease. Ann Rheum Dis 69:1502–1510PubMed
72.
go back to reference Blanco FJ, Rego I, Ruiz-Romero C (2011) The role of mitochondria in osteoarthritis. Nat Rev Rheumatol 7:161–169PubMed Blanco FJ, Rego I, Ruiz-Romero C (2011) The role of mitochondria in osteoarthritis. Nat Rev Rheumatol 7:161–169PubMed
73.
go back to reference Yang X, Chen W, Zhao X, Chen L, Li W, Ran J, Wu L (2018) Pyruvate kinase M2 modulates the glycolysis of chondrocyte and extracellular matrix in osteoarthritis. DNA Cell Biol 37:271–277PubMed Yang X, Chen W, Zhao X, Chen L, Li W, Ran J, Wu L (2018) Pyruvate kinase M2 modulates the glycolysis of chondrocyte and extracellular matrix in osteoarthritis. DNA Cell Biol 37:271–277PubMed
74.
go back to reference Liu-Bryan R, Terkeltaub R (2015) Emerging regulators of the inflammatory process in osteoarthritis. Nat Rev Rheumatol 11:35–44PubMed Liu-Bryan R, Terkeltaub R (2015) Emerging regulators of the inflammatory process in osteoarthritis. Nat Rev Rheumatol 11:35–44PubMed
75.
go back to reference Qu J, Lu D, Guo H, Miao W, Wu G, Zhou M (2016) PFKFB3 modulates glycolytic metabolism and alleviates endoplasmic reticulum stress in human osteoarthritis cartilage. Clin Exp Pharmacol Physiol 43:312–318PubMed Qu J, Lu D, Guo H, Miao W, Wu G, Zhou M (2016) PFKFB3 modulates glycolytic metabolism and alleviates endoplasmic reticulum stress in human osteoarthritis cartilage. Clin Exp Pharmacol Physiol 43:312–318PubMed
76.
go back to reference Tchetina EV, Poole AR, Zaitseva EM, Sharapova EP, Kashevarova NG, Taskina EA, Alekseeva LI, Semyonova LA, Glukhova SI, Kuzin AN, Makarov MA, Makarov SA (2013) Differences in Mammalian target of rapamycin gene expression in the peripheral blood and articular cartilages of osteoarthritic patients and disease activity. Arthritis 2013:461486PubMedPubMedCentral Tchetina EV, Poole AR, Zaitseva EM, Sharapova EP, Kashevarova NG, Taskina EA, Alekseeva LI, Semyonova LA, Glukhova SI, Kuzin AN, Makarov MA, Makarov SA (2013) Differences in Mammalian target of rapamycin gene expression in the peripheral blood and articular cartilages of osteoarthritic patients and disease activity. Arthritis 2013:461486PubMedPubMedCentral
77.
go back to reference Alvarez-Garcia O, Matsuzaki T, Olmer M, Plate L, Kelly JW, Lotz MK (2017) Regulated in development and DNA damage response 1 deficiency impairs autophagy and mitochondrial biogenesis in articular cartilage and increases the severity of experimental osteoarthritis. Arthritis Rheumatol 69:1418–1428PubMedPubMedCentral Alvarez-Garcia O, Matsuzaki T, Olmer M, Plate L, Kelly JW, Lotz MK (2017) Regulated in development and DNA damage response 1 deficiency impairs autophagy and mitochondrial biogenesis in articular cartilage and increases the severity of experimental osteoarthritis. Arthritis Rheumatol 69:1418–1428PubMedPubMedCentral
78.
go back to reference Vasheghani F, Zhang Y, Li YH, Blati M, Fahmi H, Lussier B, Roughley P, Lagares D, Endisha H, Saffar B, Lajeunesse D, Marshall WK, Rampersaud YR, Mahomed NN, Gandhi R, Pelletier JP, Martel-Pelletier J, Kapoor M (2015) PPARγ deficiency results in severe, accelerated osteoarthritis associated with aberrant mTOR signalling in the articular cartilage. Ann Rheum Dis 74:569–578PubMed Vasheghani F, Zhang Y, Li YH, Blati M, Fahmi H, Lussier B, Roughley P, Lagares D, Endisha H, Saffar B, Lajeunesse D, Marshall WK, Rampersaud YR, Mahomed NN, Gandhi R, Pelletier JP, Martel-Pelletier J, Kapoor M (2015) PPARγ deficiency results in severe, accelerated osteoarthritis associated with aberrant mTOR signalling in the articular cartilage. Ann Rheum Dis 74:569–578PubMed
79.
go back to reference Xue JF, Shi ZM, Zou J, Li XL (2017) Inhibition of PI3K/AKT/mTOR signaling pathway promotes autophagy of articular chondrocytes and attenuates inflammatory response in rats with osteoarthritis. Biomed Pharmacother 89:1252–1261PubMed Xue JF, Shi ZM, Zou J, Li XL (2017) Inhibition of PI3K/AKT/mTOR signaling pathway promotes autophagy of articular chondrocytes and attenuates inflammatory response in rats with osteoarthritis. Biomed Pharmacother 89:1252–1261PubMed
80.
go back to reference Chang SF, Huang KC, Cheng CC, Su YP, Lee KC, Chen CN, Chang HI (2017) Glucose adsorption to chitosan membranes increases proliferation of human chondrocyte via mammalian target of rapamycin complex 1 and sterol regulatory element-binding protein-1 signaling. J Cell Physiol 232:2741–2749PubMed Chang SF, Huang KC, Cheng CC, Su YP, Lee KC, Chen CN, Chang HI (2017) Glucose adsorption to chitosan membranes increases proliferation of human chondrocyte via mammalian target of rapamycin complex 1 and sterol regulatory element-binding protein-1 signaling. J Cell Physiol 232:2741–2749PubMed
81.
go back to reference Chen J, Crawford R, Xiao Y (2013) Vertical inhibition of the PI3K/Akt/mTOR pathway for the treatment of osteoarthritis. J Cell Biochem 114:245–249PubMed Chen J, Crawford R, Xiao Y (2013) Vertical inhibition of the PI3K/Akt/mTOR pathway for the treatment of osteoarthritis. J Cell Biochem 114:245–249PubMed
82.
go back to reference Lin C, Shao Y, Zeng C, Zhao C, Fang H, Wang L, Pan J, Liu L, Qi W, Feng X, Qiu H, Zhang H, Chen Y, Wang H, Cai D, Xian CJ (2018) Blocking PI3K/AKT signaling inhibits bone sclerosis in subchondral bone and attenuates post-traumatic osteoarthritis. J Cell Physiol 233:6135–6147PubMed Lin C, Shao Y, Zeng C, Zhao C, Fang H, Wang L, Pan J, Liu L, Qi W, Feng X, Qiu H, Zhang H, Chen Y, Wang H, Cai D, Xian CJ (2018) Blocking PI3K/AKT signaling inhibits bone sclerosis in subchondral bone and attenuates post-traumatic osteoarthritis. J Cell Physiol 233:6135–6147PubMed
83.
go back to reference Li D, Wu Z, Duan Y, Hao D, Zhang X, Luo H, Chen B, Qiu G (2012) TNFα-mediated apoptosis in human osteoarthritic chondrocytes sensitized by PI3K-NF-κB inhibitor, not mTOR inhibitor. Rheumatol Int 32:2017–2022PubMed Li D, Wu Z, Duan Y, Hao D, Zhang X, Luo H, Chen B, Qiu G (2012) TNFα-mediated apoptosis in human osteoarthritic chondrocytes sensitized by PI3K-NF-κB inhibitor, not mTOR inhibitor. Rheumatol Int 32:2017–2022PubMed
84.
go back to reference Rosa SC, Rufino AT, Judas F, Tenreiro C, Lopes MC, Mendes AF (2011) Expression and function of the insulin receptor in normal and osteoarthritic human chondrocytes: modulation of anabolic gene expression, glucose transport and GLUT-1 content by insulin. Osteoarthr Cartil 19:719–727 Rosa SC, Rufino AT, Judas F, Tenreiro C, Lopes MC, Mendes AF (2011) Expression and function of the insulin receptor in normal and osteoarthritic human chondrocytes: modulation of anabolic gene expression, glucose transport and GLUT-1 content by insulin. Osteoarthr Cartil 19:719–727
85.
go back to reference Pfander D, Cramer T, Swoboda B (2005) Hypoxia and HIF-1alpha in osteoarthritis. Int Orthop 29:6–9PubMed Pfander D, Cramer T, Swoboda B (2005) Hypoxia and HIF-1alpha in osteoarthritis. Int Orthop 29:6–9PubMed
86.
go back to reference Fernández-Torres J, Zamudio-Cuevas Y, Martínez-Nava GA, López-Reyes AG (2017) Hypoxia-inducible factors (HIFs) in the articular cartilage: a systematic review. Eur Rev Med Pharmacol Sci 21:2800–2810PubMed Fernández-Torres J, Zamudio-Cuevas Y, Martínez-Nava GA, López-Reyes AG (2017) Hypoxia-inducible factors (HIFs) in the articular cartilage: a systematic review. Eur Rev Med Pharmacol Sci 21:2800–2810PubMed
87.
go back to reference Ishizuka S, Sakai T, Hiraiwa H, Hamada T, Knudson W, Omachi T, Ono Y, Nakashima M, Matsukawa T, Oda T, Takamatsu A, Yamashita S, Ishiguro N (2016) Hypoxia-inducible factor-2α induces expression of type X collagen and matrix metalloproteinases 13 in osteoarthritic meniscal cells. Inflamm Res 65:439–448PubMed Ishizuka S, Sakai T, Hiraiwa H, Hamada T, Knudson W, Omachi T, Ono Y, Nakashima M, Matsukawa T, Oda T, Takamatsu A, Yamashita S, Ishiguro N (2016) Hypoxia-inducible factor-2α induces expression of type X collagen and matrix metalloproteinases 13 in osteoarthritic meniscal cells. Inflamm Res 65:439–448PubMed
88.
go back to reference Rankin EB, Giaccia AJ, Schipani E (2011) A central role for hypoxic signaling in cartilage, bone, and hematopoiesis. Curr Osteoporos Rep 9:46–52PubMedPubMedCentral Rankin EB, Giaccia AJ, Schipani E (2011) A central role for hypoxic signaling in cartilage, bone, and hematopoiesis. Curr Osteoporos Rep 9:46–52PubMedPubMedCentral
89.
go back to reference Qing L, Lei P, Liu H, Xie J, Wang L, Wen T, Hu Y (2014) Expression of hypoxia-inducible factor-1α in synovial fluid and articular cartilage is associated with disease severity in knee osteoarthritis. Exp Ther Med 13:63–68 Qing L, Lei P, Liu H, Xie J, Wang L, Wen T, Hu Y (2014) Expression of hypoxia-inducible factor-1α in synovial fluid and articular cartilage is associated with disease severity in knee osteoarthritis. Exp Ther Med 13:63–68
90.
go back to reference Chu H, Xu ZM, Yu H, Zhu KJ, Huang H (2013) Association between hypoxia-inducible factor-1a levels in serum and synovial fluid with the radiographic severity of knee osteoarthritis. Genet Mol Res 13:10529–10536 Chu H, Xu ZM, Yu H, Zhu KJ, Huang H (2013) Association between hypoxia-inducible factor-1a levels in serum and synovial fluid with the radiographic severity of knee osteoarthritis. Genet Mol Res 13:10529–10536
91.
go back to reference Markway BD, Cho H, Johnstone B (2013) Hypoxia promotes redifferentiation and suppresses markers of hypertrophy and degeneration in both healthy and osteoarthritic chondrocytes. Arthritis Res Ther 15:R92PubMedPubMedCentral Markway BD, Cho H, Johnstone B (2013) Hypoxia promotes redifferentiation and suppresses markers of hypertrophy and degeneration in both healthy and osteoarthritic chondrocytes. Arthritis Res Ther 15:R92PubMedPubMedCentral
92.
go back to reference Gouttenoire J, Valcourt U, Ronzière MC, Aubert-Foucher E, Mallein-Gerin F, Herbage D (2004) Modulation of collagen synthesis in normal and osteoarthritic cartilage. Biorheology 41:535–542PubMed Gouttenoire J, Valcourt U, Ronzière MC, Aubert-Foucher E, Mallein-Gerin F, Herbage D (2004) Modulation of collagen synthesis in normal and osteoarthritic cartilage. Biorheology 41:535–542PubMed
93.
go back to reference Zhou J, Wei X, Wei L (2014) Indian Hedgehog, a critical modulator in osteoarthritis, could be a potential therapeutic target for attenuating cartilage degeneration disease. Connect Tissue Res 55:257–261PubMed Zhou J, Wei X, Wei L (2014) Indian Hedgehog, a critical modulator in osteoarthritis, could be a potential therapeutic target for attenuating cartilage degeneration disease. Connect Tissue Res 55:257–261PubMed
94.
go back to reference Li R, Cai L, Ding J, Hu CM, Wu TN, Hu XY (2015) Inhibition of hedgehog signal pathway by cyclopamine attenuates inflammation and articular cartilage damage in rats with adjuvant-induced arthritis. J Pharm Pharmacol 67:963–971PubMed Li R, Cai L, Ding J, Hu CM, Wu TN, Hu XY (2015) Inhibition of hedgehog signal pathway by cyclopamine attenuates inflammation and articular cartilage damage in rats with adjuvant-induced arthritis. J Pharm Pharmacol 67:963–971PubMed
95.
go back to reference Pelletier JP, Faure MP, DiBattista JA, Wilhelm S, Visco D, Martel-Pelletier J (1993) Coordinate synthesis of stromelysin, interleukin-1, and oncogene proteins in experimental osteoarthritis. An immunohistochemical study. Am J Pathol 142:95–105PubMedPubMedCentral Pelletier JP, Faure MP, DiBattista JA, Wilhelm S, Visco D, Martel-Pelletier J (1993) Coordinate synthesis of stromelysin, interleukin-1, and oncogene proteins in experimental osteoarthritis. An immunohistochemical study. Am J Pathol 142:95–105PubMedPubMedCentral
96.
go back to reference Yatsugi N, Tsukazaki T, Osaki M, Koji T, Yamashita S, Shindo H (2000) Apoptosis of articular chondrocytes in rheumatoid arthritis and osteoarthritis: correlation of apoptosis with degree of cartilage destruction and expression of apoptosis-related proteins of p53 and c-myc. J Orthop Sci 5:150–156PubMed Yatsugi N, Tsukazaki T, Osaki M, Koji T, Yamashita S, Shindo H (2000) Apoptosis of articular chondrocytes in rheumatoid arthritis and osteoarthritis: correlation of apoptosis with degree of cartilage destruction and expression of apoptosis-related proteins of p53 and c-myc. J Orthop Sci 5:150–156PubMed
97.
go back to reference Zhou Y, Tao H, Li Y, Deng M, He B, Xia S, Zhang C, Liu S (2016) Berberine promotes proliferation of sodium nitroprusside-stimulated rat chondrocytes and osteoarthritic rat cartilage via Wnt/β-catenin pathway. Eur J Pharmacol 789:109–118PubMed Zhou Y, Tao H, Li Y, Deng M, He B, Xia S, Zhang C, Liu S (2016) Berberine promotes proliferation of sodium nitroprusside-stimulated rat chondrocytes and osteoarthritic rat cartilage via Wnt/β-catenin pathway. Eur J Pharmacol 789:109–118PubMed
98.
go back to reference Dvir-Ginzberg M, Steinmeyer J (2013) Towards elucidating the role of SirT1 in osteoarthritis. Front Biosci 18:343e55 Dvir-Ginzberg M, Steinmeyer J (2013) Towards elucidating the role of SirT1 in osteoarthritis. Front Biosci 18:343e55
99.
go back to reference Gabay O, Oppenhiemer H, Meir H, Zaal K, Sanchez C, Dvir-Ginzberg M (2012) Increased apoptotic chondrocytes in articular cartilage from adult heterozygous SirT1 mice. Ann Rheum Dis 71:613–616PubMed Gabay O, Oppenhiemer H, Meir H, Zaal K, Sanchez C, Dvir-Ginzberg M (2012) Increased apoptotic chondrocytes in articular cartilage from adult heterozygous SirT1 mice. Ann Rheum Dis 71:613–616PubMed
100.
go back to reference Dvir-Ginzberg M, Gagarina V, Lee EJ, Hall DJ (2008) Regulation of cartilage-specific gene expression in human chondrocytes by SirT1 and nicotinamide phosphoribosyltransferase. J Biol Chem 283:36300e10 Dvir-Ginzberg M, Gagarina V, Lee EJ, Hall DJ (2008) Regulation of cartilage-specific gene expression in human chondrocytes by SirT1 and nicotinamide phosphoribosyltransferase. J Biol Chem 283:36300e10
101.
go back to reference Wu Y, Chen L, Wang Y, Li W, Lin Y, Yu D, Zhang L, Li F, Pan Z (2015) Overexpression of Sirtuin 6 suppresses cellular senescence and NF-κB mediated inflammatory responses in osteoarthritis development. Sci Rep 5:17602PubMedPubMedCentral Wu Y, Chen L, Wang Y, Li W, Lin Y, Yu D, Zhang L, Li F, Pan Z (2015) Overexpression of Sirtuin 6 suppresses cellular senescence and NF-κB mediated inflammatory responses in osteoarthritis development. Sci Rep 5:17602PubMedPubMedCentral
102.
go back to reference Matsuzaki T, Matsushita T, Takayama K, Matsumoto T, Nishida K, Kuroda R, Kurosaka M (2014) Disruption of Sirt1 in chondrocytes causes accelerated progression of osteoarthritis under mechanical stress and during ageing in mice. Ann Rheum Dis 73:1397–1404PubMed Matsuzaki T, Matsushita T, Takayama K, Matsumoto T, Nishida K, Kuroda R, Kurosaka M (2014) Disruption of Sirt1 in chondrocytes causes accelerated progression of osteoarthritis under mechanical stress and during ageing in mice. Ann Rheum Dis 73:1397–1404PubMed
103.
go back to reference Gabay O, Sanchez C, Dvir-Ginzberg M, Gaqarina V, Zaal KJ, Song Y, He XH, McBurney MW (2013) Sirt1 enzymatic activity is required for cartilage homeostasis in vivo. Arthritis Rheum 65:159–166PubMedPubMedCentral Gabay O, Sanchez C, Dvir-Ginzberg M, Gaqarina V, Zaal KJ, Song Y, He XH, McBurney MW (2013) Sirt1 enzymatic activity is required for cartilage homeostasis in vivo. Arthritis Rheum 65:159–166PubMedPubMedCentral
104.
go back to reference Moon MH, Jeong JK, Lee YJ, Seol JW, Jackson CJ, Park SY (2013) SIRT1, a class III histone deacetylase, regulates TNFα-induced inflammation in human chondrocytes. Osteoarthr Cartil 21:470–480 Moon MH, Jeong JK, Lee YJ, Seol JW, Jackson CJ, Park SY (2013) SIRT1, a class III histone deacetylase, regulates TNFα-induced inflammation in human chondrocytes. Osteoarthr Cartil 21:470–480
105.
go back to reference Igarashi M, Sakamoto K, Nagaoka I (2017) Effect of glucosamine on expression of type II collagen, matrix metalloproteinase and sirtuin genes in a human chondrocyte cell line. Int J Mol Med 39:472–478PubMed Igarashi M, Sakamoto K, Nagaoka I (2017) Effect of glucosamine on expression of type II collagen, matrix metalloproteinase and sirtuin genes in a human chondrocyte cell line. Int J Mol Med 39:472–478PubMed
106.
go back to reference Yang S, Ryu JH, Oh H, Jeon J, Kwak JS, Kim JH, Kim HA, Chun CH, Chun JS (2015) NAMPT (visfatin), a direct target of hypoxia-inducible factor-2α, is an essential catabolic regulator of osteoarthritis. Ann Rheum Dis 74:595–602PubMed Yang S, Ryu JH, Oh H, Jeon J, Kwak JS, Kim JH, Kim HA, Chun CH, Chun JS (2015) NAMPT (visfatin), a direct target of hypoxia-inducible factor-2α, is an essential catabolic regulator of osteoarthritis. Ann Rheum Dis 74:595–602PubMed
107.
go back to reference Terauchi K, Kobayashi H, Yatabe K, Yui N, Fujiya H, Niki H, Musha H, Yudoh K (2016) The NAD-dependent deacetylase sirtuin-1 regulates the expression of osteogenic transcriptional activator runt-related transcription factor 2 (Runx2) and production of matrix metalloproteinase (MMP)-13 in chondrocytes in osteoarthritis. Int J Mol Sci 17:1019PubMedCentral Terauchi K, Kobayashi H, Yatabe K, Yui N, Fujiya H, Niki H, Musha H, Yudoh K (2016) The NAD-dependent deacetylase sirtuin-1 regulates the expression of osteogenic transcriptional activator runt-related transcription factor 2 (Runx2) and production of matrix metalloproteinase (MMP)-13 in chondrocytes in osteoarthritis. Int J Mol Sci 17:1019PubMedCentral
108.
go back to reference Terkeltaub R, Yang B, Lotz M, Liu-Bryan R (2011) Chondrocyte AMP-activated protein kinase activity suppresses matrix degradation responses to proinflammatory cytokines interleukin-1beta and tumor necrosis factor alpha. Arthritis Rheum 63:1928–1937PubMedPubMedCentral Terkeltaub R, Yang B, Lotz M, Liu-Bryan R (2011) Chondrocyte AMP-activated protein kinase activity suppresses matrix degradation responses to proinflammatory cytokines interleukin-1beta and tumor necrosis factor alpha. Arthritis Rheum 63:1928–1937PubMedPubMedCentral
109.
go back to reference Wang Y, Zhao X, Lotz M, Terkeltaub R, Liu-Bryan R (2015) Mitochondrial biogenesis is impaired in osteoarthritis chondrocytes but reversible via peroxisome proliferator-activated receptor gamma coactivator 1alpha. Arthritis Rheumatol 67:2141–2153PubMedPubMedCentral Wang Y, Zhao X, Lotz M, Terkeltaub R, Liu-Bryan R (2015) Mitochondrial biogenesis is impaired in osteoarthritis chondrocytes but reversible via peroxisome proliferator-activated receptor gamma coactivator 1alpha. Arthritis Rheumatol 67:2141–2153PubMedPubMedCentral
110.
go back to reference Zhou S, Lu W, Chen L, Ge Q, Chen D, Xu Z, Shi D, Dai J, Li J, Ju H, Cao Y, Qin J, Chen S, Teng H, Jiang Q (2017) AMPK deficiency in chondrocytes accelerated the progression of instability-induced and ageing-associated osteoarthritis in adult mice. Sci Rep 7:43245PubMedPubMedCentral Zhou S, Lu W, Chen L, Ge Q, Chen D, Xu Z, Shi D, Dai J, Li J, Ju H, Cao Y, Qin J, Chen S, Teng H, Jiang Q (2017) AMPK deficiency in chondrocytes accelerated the progression of instability-induced and ageing-associated osteoarthritis in adult mice. Sci Rep 7:43245PubMedPubMedCentral
111.
go back to reference Tchetina EV, Markova GA, Poole AR, Zukor DJ, Antoniou J, Makarov SA, Kuzin AN (2016) Deferoxamine suppresses collagen cleavage and protease, Cytokine, and COL10A1 expression and upregulates AMPK and Krebs cycle genes in human osteoarthritic cartilage. Int J Rheumatol 2016:6432867PubMedPubMedCentral Tchetina EV, Markova GA, Poole AR, Zukor DJ, Antoniou J, Makarov SA, Kuzin AN (2016) Deferoxamine suppresses collagen cleavage and protease, Cytokine, and COL10A1 expression and upregulates AMPK and Krebs cycle genes in human osteoarthritic cartilage. Int J Rheumatol 2016:6432867PubMedPubMedCentral
112.
go back to reference Al-Khazraji BK, Appleton CT, Beier F, Birmingham TB, Shoemaker JK (2018) Osteoarthritis, cerebrovascular dysfunction and the common denominator of inflammation: a narrative review. Osteoarthr Cartil 26:462–470 Al-Khazraji BK, Appleton CT, Beier F, Birmingham TB, Shoemaker JK (2018) Osteoarthritis, cerebrovascular dysfunction and the common denominator of inflammation: a narrative review. Osteoarthr Cartil 26:462–470
113.
go back to reference Attur M, Krasnokutsky S, Statnikov A, Samuels J, Li Z, Friese O, Graverand-Gastineau HL, Rybak MP, Kraus L, Jordan VB, Aliferis JM, Abramson CF SB (2015) Low-grade inflammation in symptomatic knee osteoarthritis: prognostic value of inflammatory plasma lipids and peripheral blood leukocyte biomarkers. Arthritis Rheumatol 67:2905–2915PubMedPubMedCentral Attur M, Krasnokutsky S, Statnikov A, Samuels J, Li Z, Friese O, Graverand-Gastineau HL, Rybak MP, Kraus L, Jordan VB, Aliferis JM, Abramson CF SB (2015) Low-grade inflammation in symptomatic knee osteoarthritis: prognostic value of inflammatory plasma lipids and peripheral blood leukocyte biomarkers. Arthritis Rheumatol 67:2905–2915PubMedPubMedCentral
114.
go back to reference Ponchel F, Burska AN, Hensor EM, Raja R, Campbell M, Emery P, Conaghan PG (2015) Changes in peripheral blood immune cell composition in osteoarthritis. Osteoarthr Cartil 23:1870–1878 Ponchel F, Burska AN, Hensor EM, Raja R, Campbell M, Emery P, Conaghan PG (2015) Changes in peripheral blood immune cell composition in osteoarthritis. Osteoarthr Cartil 23:1870–1878
115.
go back to reference Kyostio-Moore S, Nambiar B, Hutto E, Ewing PJ, Piraino S, Berthelette P, Sookdeo C, Matthews G, Armentano D (2011) STR/ort mice, a model for spontaneous osteoarthritis, exhibit elevated levels of both local and systemic inflammatory markers. Comp Med 61:346–355PubMedPubMedCentral Kyostio-Moore S, Nambiar B, Hutto E, Ewing PJ, Piraino S, Berthelette P, Sookdeo C, Matthews G, Armentano D (2011) STR/ort mice, a model for spontaneous osteoarthritis, exhibit elevated levels of both local and systemic inflammatory markers. Comp Med 61:346–355PubMedPubMedCentral
116.
go back to reference Attur M, Belitskaya-Lévy I, Oh C, Krasnokutsky S, Greenberg J, Samuels J, Smiles S, Lee S, Patel J, Al-Mussawir H, McDaniel G, Kraus VB, Abramson SB (2011) Increased interleukin-1β gene expression in peripheral blood leukocytes is associated with increased pain and predicts risk for progression of symptomatic knee osteoarthritis. Arthritis Rheum 63:1908–1917PubMedPubMedCentral Attur M, Belitskaya-Lévy I, Oh C, Krasnokutsky S, Greenberg J, Samuels J, Smiles S, Lee S, Patel J, Al-Mussawir H, McDaniel G, Kraus VB, Abramson SB (2011) Increased interleukin-1β gene expression in peripheral blood leukocytes is associated with increased pain and predicts risk for progression of symptomatic knee osteoarthritis. Arthritis Rheum 63:1908–1917PubMedPubMedCentral
117.
go back to reference Sowers MR, Karvonen-Gutierrez CA (2010) The evolving role of obesity in knee osteoarthritis. Curr Opin Rheumatol 22:533–537PubMedPubMedCentral Sowers MR, Karvonen-Gutierrez CA (2010) The evolving role of obesity in knee osteoarthritis. Curr Opin Rheumatol 22:533–537PubMedPubMedCentral
118.
go back to reference Gegout PP, Francin PJ, Mainard D, Presle N (2010) Adipokines in osteoarthritis: friends or foes of cartilage homeostasis? Jt Bone Spine 75:669–671 Gegout PP, Francin PJ, Mainard D, Presle N (2010) Adipokines in osteoarthritis: friends or foes of cartilage homeostasis? Jt Bone Spine 75:669–671
119.
go back to reference Gabay O, Hall DJ, Berenbaum F, Henrotin Y, Sanchez C (2008) Osteoarthritis and obesity: experimental models. Jt Bone Spine 75:675–679 Gabay O, Hall DJ, Berenbaum F, Henrotin Y, Sanchez C (2008) Osteoarthritis and obesity: experimental models. Jt Bone Spine 75:675–679
120.
go back to reference Laiguillon MC, Houard X, Bougault C, Gosset M, Nourissat G, Sautet A, Jacques C, Berenbaum F, Sellam J (2014) Expression and function of visfatin (Nampt), an adipokine-enzyme involved in inflammatory pathways of osteoarthritis. Arthritis Res Ther 16(1):R38PubMedPubMedCentral Laiguillon MC, Houard X, Bougault C, Gosset M, Nourissat G, Sautet A, Jacques C, Berenbaum F, Sellam J (2014) Expression and function of visfatin (Nampt), an adipokine-enzyme involved in inflammatory pathways of osteoarthritis. Arthritis Res Ther 16(1):R38PubMedPubMedCentral
121.
go back to reference Chen WP, Bao JP, Feng J, Hu PF, Shi ZL, Wu LD (2010) Increased serum concentrations of visfatin and its production by different joint tissues in patients with osteoarthritis. Clin Chem Lab Med 48:1141–1145PubMed Chen WP, Bao JP, Feng J, Hu PF, Shi ZL, Wu LD (2010) Increased serum concentrations of visfatin and its production by different joint tissues in patients with osteoarthritis. Clin Chem Lab Med 48:1141–1145PubMed
122.
go back to reference Calvet J, Orellana C, Gratacós J, Berenguer-Llergo A, Caixàs A, Chillarón JJ, Pedro-Botet J, García-Manrique M, Navarro N, Larrosa M (2016) Synovial fluid adipokines are associated with clinical severity in knee osteoarthritis: a cross-sectional study in female patients with joint effusion. Arthritis Res Ther 18(1):207PubMedPubMedCentral Calvet J, Orellana C, Gratacós J, Berenguer-Llergo A, Caixàs A, Chillarón JJ, Pedro-Botet J, García-Manrique M, Navarro N, Larrosa M (2016) Synovial fluid adipokines are associated with clinical severity in knee osteoarthritis: a cross-sectional study in female patients with joint effusion. Arthritis Res Ther 18(1):207PubMedPubMedCentral
123.
go back to reference Duan Y, Hao D, Li M, Wu Z, Li D, Yang X, Qiu G (2012) Increased synovial fluid visfatin is positively linked to cartilage degradation biomarkers in osteoarthritis. Rheumatol Int 32:985–990PubMed Duan Y, Hao D, Li M, Wu Z, Li D, Yang X, Qiu G (2012) Increased synovial fluid visfatin is positively linked to cartilage degradation biomarkers in osteoarthritis. Rheumatol Int 32:985–990PubMed
124.
go back to reference Fioravanti A, Cheleschi S, De Palma A, Addimanda O, Mancarella L, Pignotti E, Pulsatelli L, Galeazzi M, Meliconi R (2018) Can adipokines serum levels be used as biomarkers of hand osteoarthritis? Biomarkers 23:265–270PubMed Fioravanti A, Cheleschi S, De Palma A, Addimanda O, Mancarella L, Pignotti E, Pulsatelli L, Galeazzi M, Meliconi R (2018) Can adipokines serum levels be used as biomarkers of hand osteoarthritis? Biomarkers 23:265–270PubMed
125.
go back to reference McNulty AL, Miller MR, O’Connor SK, Guilak F (2011) The effects of adipokines on cartilage and meniscus catabolism. Connect Tissue Res 52:523–533PubMedPubMedCentral McNulty AL, Miller MR, O’Connor SK, Guilak F (2011) The effects of adipokines on cartilage and meniscus catabolism. Connect Tissue Res 52:523–533PubMedPubMedCentral
127.
go back to reference Shi LZ, Wang R, Huang G, Vogel P, Neale G, Green DR, Chi H (2011) HIF1alpha-dependent glycolytic pathway orchestrates a metabolic checkpoint for the differentiation of TH17 and Treg cells. J Exp Med 208:1367–1376PubMedPubMedCentral Shi LZ, Wang R, Huang G, Vogel P, Neale G, Green DR, Chi H (2011) HIF1alpha-dependent glycolytic pathway orchestrates a metabolic checkpoint for the differentiation of TH17 and Treg cells. J Exp Med 208:1367–1376PubMedPubMedCentral
128.
go back to reference Zhou L, Lopes JE, Chong MM, Ivanov II, Min R, Victora GD, Shen Y, Du J, Rubtsov YP, Rudensky AY, Ziegler SF, Littman DR (2008) TGF-beta-induced Foxp3 inhibits T(H)17 cell differentiation by antagonizing RORgamma function. Nature 453:236–240PubMedPubMedCentral Zhou L, Lopes JE, Chong MM, Ivanov II, Min R, Victora GD, Shen Y, Du J, Rubtsov YP, Rudensky AY, Ziegler SF, Littman DR (2008) TGF-beta-induced Foxp3 inhibits T(H)17 cell differentiation by antagonizing RORgamma function. Nature 453:236–240PubMedPubMedCentral
129.
go back to reference Straub RH, Cutolo M, Buttgereit F, Pongratz G (2010) Energy regulation and neuroendocrine-immune control in chronic inflammatory diseases. J Intern Med 267:543–560PubMed Straub RH, Cutolo M, Buttgereit F, Pongratz G (2010) Energy regulation and neuroendocrine-immune control in chronic inflammatory diseases. J Intern Med 267:543–560PubMed
Metadata
Title
Regulation of energy metabolism in the growth plate and osteoarthritic chondrocytes
Authors
Elena V. Tchetina
Galina A. Markova
Publication date
01-11-2018
Publisher
Springer Berlin Heidelberg
Published in
Rheumatology International / Issue 11/2018
Print ISSN: 0172-8172
Electronic ISSN: 1437-160X
DOI
https://doi.org/10.1007/s00296-018-4103-4

Other articles of this Issue 11/2018

Rheumatology International 11/2018 Go to the issue