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Current Rheumatology Reports
Published in: Current Rheumatology Reports 3/2015

Open Access 01-03-2015 | Osteoarthritis (MB Goldring, Section Editor)

Physicochemical and Biomechanical Stimuli in Cell-Based Articular Cartilage Repair

Authors: Holger Jahr, Csaba Matta, Ali Mobasheri

Published in: Current Rheumatology Reports | Issue 3/2015

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Abstract

Articular cartilage is a unique load-bearing connective tissue with a low intrinsic capacity for repair and regeneration. Its avascularity makes it relatively hypoxic and its unique extracellular matrix is enriched with cations, which increases the interstitial fluid osmolarity. Several physicochemical and biomechanical stimuli are reported to influence chondrocyte metabolism and may be utilized for regenerative medical approaches. In this review article, we summarize the most relevant stimuli and describe how ion channels may contribute to cartilage homeostasis, with special emphasis on intracellular signaling pathways. We specifically focus on the role of calcium signaling as an essential mechanotransduction component and highlight the role of phosphatase signaling in this context.
Literature
1.
Mow VC, Ratcliffe A, Poole AR. Cartilage and diarthrodial joints as paradigms for hierarchical materials and structures. Biomaterials. 1992;13(2):67–97.PubMed
2.
Lesperance LM, Gray ML, Burstein D. Determination of fixed charge density in cartilage using nuclear magnetic resonance. J Orthop Res. 1992;10(1):1–13.PubMed
3.
Mow VCYGW, Hui CF. Structure and function of articular cartilage and meniscus. Basic orthopaedic biomechanics and mechanobiology. Philadelphia (PA): Lippincott Williams & Wilkins; 2005.
4.
Mow VC, Ateshian GA, Spilker RL. Biomechanics of diarthrodial joints: a review of twenty years of progress. J Biomech Eng. 1993;115(4B):460–7.PubMed
5.
Maroudas AI. Balance between swelling pressure and collagen tension in normal and degenerate cartilage. Nature. 1976;260(5554):808–9.PubMed
6.
Lai WM, Mow VC, Sun DD, Ateshian GA. On the electric potentials inside a charged soft hydrated biological tissue: streaming potential versus diffusion potential. J Biomech Eng. 2000;122(4):336–46.PubMed
7.
Bassett CA, Pawluk RJ. Electrical behavior of cartilage during loading. Science. 1972;178(4064):982–3.PubMed
8.
Buschmann MD, Grodzinsky AJ. A molecular model of proteoglycan-associated electrostatic forces in cartilage mechanics. J Biomech Eng. 1995;117(2):179–92.PubMed
9.
Chen AC, Nguyen TT, Sah RL. Streaming potentials during the confined compression creep test of normal and proteoglycan-depleted cartilage. Ann Biomed Eng. 1997;25(2):269–77.PubMed
10.
Mow VC, Guo XE. Mechano-electrochemical properties of articular cartilage: their inhomogeneities and anisotropies. Annu Rev Biomed Eng. 2002;4:175–209.PubMed
11.
Mow VC, Wang CC, Hung CT. The extracellular matrix, interstitial fluid and ions as a mechanical signal transducer in articular cartilage. Osteoarthr Cartil. 1999;7(1):41–58.PubMed
12.
Little CJ, Bawolin NK, Chen X. Mechanical properties of natural cartilage and tissue-engineered constructs. Tissue Eng B Rev. 2011;17(4):213–27.
13.
Smith GD, Knutsen G, Richardson JB. A clinical review of cartilage repair techniques. J Bone Joint Surg (Br). 2005;87(4):445–9.
14.
Domarad BR, Buschmann MT. Interviewing older adults: increasing the credibility of interview data. J Gerontol Nurs. 1995;21(9):14–20.PubMed
15.
Jordan MA, Van Thiel GS, Chahal J, Nho SJ. Operative treatment of chondral defects in the hip joint: a systematic review. Curr Rev Musculoskelet Med. 2012;5(3):244–53.PubMedCentralPubMed
16.
Zhang W, Moskowitz RW, Nuki G, Abramson S, Altman RD, Arden N, et al. OARSI recommendations for the management of hip and knee osteoarthritis, part I: critical appraisal of existing treatment guidelines and systematic review of current research evidence. Osteoarthr Cart. 2007;15(9):981–1000.
17.
Heinegard D, Saxne T. The role of the cartilage matrix in osteoarthritis. Nat Rev Rheumatol. 2011;7(1):50–6.PubMed
18.•
Brady MA, Waldman SD, Ethier CR. The Application of multiple biophysical cues to engineer functional neo-cartilage for treatment of osteoarthritis (part I: cellular response). Tissue Eng Part B Rev. 2014. This recent paper highlights the fact that tissue engineering strategies and the development of “smart” functionalized biomaterials that enable the delivery of growth factors or integration of conjugated nanoparticles may benefit from targeting known signal transduction pathways in combination with external biophysical cues.
19.
Grodzinsky AJ, Levenston ME, Jin M, Frank EH. Cartilage tissue remodeling in response to mechanical forces. Annu Rev Biomed Eng. 2000;2:691–713.PubMed
20.
Bondeson J, Wainwright S, Hughes C, Caterson B. The regulation of the ADAMTS4 and ADAMTS5 aggrecanases in osteoarthritis: a review. Clin Exp Rheumatol. 2008;26(1):139–45.PubMed
21.
Malemud CJ, Papay RS, Hering TM, Holderbaum D, Goldberg VM, Haqqi TM. Phenotypic modulation of newly synthesized proteoglycans in human cartilage and chondrocytes. Osteoarthr Cart. 1995;3(4):227–38.
22.
Nelson F, Billinghurst RC, Pidoux I, Reiner A, Langworthy M, McDermott M, et al. Early post-traumatic osteoarthritis-like changes in human articular cartilage following rupture of the anterior cruciate ligament. Osteoarthr Cart. 2006;14(2):114–9.
23.
Williamson AK, Chen AC, Sah RL. Compressive properties and function-composition relationships of developing bovine articular cartilage. J Orthop Res. 2001;19(6):1113–21.PubMed
24.
Bank RA, Soudry M, Maroudas A, Mizrahi J, TeKoppele JM. The increased swelling and instantaneous deformation of osteoarthritic cartilage is highly correlated with collagen degradation. Arthritis Rheum. 2000;43(10):2202–10.PubMed
25.
Brittberg M, Lindahl A, Nilsson A, Ohlsson C, Isaksson O, Peterson L. Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. N Engl J Med. 1994;331(14):889–95.PubMed
26.
Saris DB, Vanlauwe J, Victor J, Haspl M, Bohnsack M, Fortems Y, et al. Characterized chondrocyte implantation results in better structural repair when treating symptomatic cartilage defects of the knee in a randomized controlled trial versus microfracture. Am J Sports Med. 2008;36(2):235–46.PubMed
27.
Kock L, van Donkelaar CC, Ito K. Tissue engineering of functional articular cartilage: the current status. Cell Tissue Res. 2012;347(3):613–27.PubMedCentralPubMed
28.
29.
Miot S, Scandiucci de Freitas P, Wirz D, Daniels AU, Sims TJ, Hollander AP, et al. Cartilage tissue engineering by expanded goat articular chondrocytes. J Orthop Res. 2006;24(5):1078–85.PubMed
30.
Waldman SD, Grynpas MD, Pilliar RM, Kandel RA. The use of specific chondrocyte populations to modulate the properties of tissue-engineered cartilage. J Orthop Res. 2003;21(1):132–8.PubMed
31.
Darling EM, Athanasiou KA. Retaining zonal chondrocyte phenotype by means of novel growth environments. Tissue Eng. 2005;11(3–4):395–403.PubMed
32.
Darling EM, Hu JC, Athanasiou KA. Zonal and topographical differences in articular cartilage gene expression. J Orthop Res. 2004;22(6):1182–7.PubMed
33.
Khan IM, Gilbert SJ, Singhrao SK, Duance VC, Archer CW. Cartilage integration: evaluation of the reasons for failure of integration during cartilage repair. A review. Eur Cell Mater. 2008;16:26–39.PubMed
34.
Gilbert SJ, Singhrao SK, Khan IM, Gonzalez LG, Thomson BM, Burdon D, et al. Enhanced tissue integration during cartilage repair in vitro can be achieved by inhibiting chondrocyte death at the wound edge. Tissue Eng A. 2009;15(7):1739–49.
35.
Snyder MJ, Wilensky JA, Fortin JD. Current applications of electrotherapeutics in collagen healing. Pain Physician. 2002;5(2):172–81.PubMed
36.
Zuzzi DC, Ciccone Cde C, Neves LM, Mendonca JS, Joazeiro PP, Esquisatto MA. Evaluation of the effects of electrical stimulation on cartilage repair in adult male rats. Tissue Cell. 2012;45(4):275–81.
37.
Balint R, Cassidy NJ, Cartmell SH. Electrical stimulation: a novel tool for tissue engineering. Tissue Eng B Rev. 2013;19(1):48–57.
38.
Armstrong PF, Brighton CT, Star AM. Capacitively coupled electrical stimulation of bovine growth plate chondrocytes grown in pellet form. J Orthop Res. 1988;6(2):265–71.PubMed
39.
Brighton CT, Jensen L, Pollack SR, Tolin BS, Clark CC. Proliferative and synthetic response of bovine growth plate chondrocytes to various capacitively coupled electrical fields. J Orthop Res. 1989;7(5):759–65.PubMed
40.
Brighton CT, Wang W, Clark CC. The effect of electrical fields on gene and protein expression in human osteoarthritic cartilage explants. J Bone Joint Surg Am. 2008;90(4):833–48.PubMed
41.
Assiotis A, Sachinis NP, Chalidis BE. Pulsed electromagnetic fields for the treatment of tibial delayed unions and nonunions. A prospective clinical study and review of the literature. J Orthop Surg Res. 2012;7:24.PubMedCentralPubMed
42.•
Hannemann PF, Mommers EH, Schots JP, Brink PR, Poeze M. The effects of low-intensity pulsed ultrasound and pulsed electromagnetic fields bone growth stimulation in acute fractures: a systematic review and meta-analysis of randomized controlled trials. Arch Orthop Trauma Surg. 2014;134(8):1093–106. doi:10.​1007/​s00402-014-2014-8. This recent paper is a systematic review and meta-analysis that suggests low-intensity pulsed ultrasound and pulsed electromagnetic fields can be beneficial in the treatment of acute fractures.PubMed
43.
Chalidis B, Sachinis N, Assiotis A, Maccauro G. Stimulation of bone formation and fracture healing with pulsed electromagnetic fields: biologic responses and clinical implications. Int J Immunopathol Pharmacol. 2011;24(1 Suppl 2):17–20.PubMed
44.
Jansen JH, van der Jagt OP, Punt BJ, Verhaar JA, van Leeuwen JP, Weinans H, et al. Stimulation of osteogenic differentiation in human osteoprogenitor cells by pulsed electromagnetic fields: an in vitro study. BMC Musculoskelet Disord. 2010;11:188.PubMedCentralPubMed
45.
Dini L, Abbro L. Bioeffects of moderate-intensity static magnetic fields on cell cultures. Micron. 2005;36(3):195–217.PubMed
46.
Fini M, Giavaresi G, Carpi A, Nicolini A, Setti S, Giardino R. Effects of pulsed electromagnetic fields on articular hyaline cartilage: review of experimental and clinical studies. Biomed Pharmacother. 2005;59(7):388–94.PubMed
47.
Vavken P, Arrich F, Schuhfried O, Dorotka R. Effectiveness of pulsed electromagnetic field therapy in the management of osteoarthritis of the knee: a meta-analysis of randomized controlled trials. J Rehabil Med. 2009;41(6):406–11.PubMed
48.
Sadoghi P, Leithner A, Dorotka R, Vavken P. Effect of pulsed electromagnetic fields on the bioactivity of human osteoarthritic chondrocytes. Orthopedics. 2013;36(3):e360–5.PubMed
49.
Fioravanti A, Nerucci F, Collodel G, Markoll R, Marcolongo R. Biochemical and morphological study of human articular chondrocytes cultivated in the presence of pulsed signal therapy. Ann Rheum Dis. 2002;61(11):1032–3.PubMedCentralPubMed
50.
Vincenzi F, Targa M, Corciulo C, Gessi S, Merighi S, Setti S, et al. Pulsed electromagnetic fields increased the anti-inflammatory effect of A(2)A and A(3) adenosine receptors in human T/C-28a2 chondrocytes and hFOB 1.19 osteoblasts. PLoS One. 2013;8(5):e65561.PubMedCentralPubMed
51.
Ongaro A, Pellati A, Masieri FF, Caruso A, Setti S, Cadossi R, et al. Chondroprotective effects of pulsed electromagnetic fields on human cartilage explants. Bioelectromagnetics. 2011;32(7):543–51.PubMed
52.
Luo Q, Li SS, He C, He H, Yang L, Deng L. Pulse electromagnetic fields effects on serum E2 levels, chondrocyte apoptosis, and matrix metalloproteinase-13 expression in ovariectomized rats. Rheumatol Int. 2009;29(8):927–35.PubMed
53.
Mizuno S, Ogawa R. Using changes in hydrostatic and osmotic pressure to manipulate metabolic function in chondrocytes. Am J Physiol Cell Physiol. 2011;300(6):C1234–45.PubMed
54.
Urban JP. The chondrocyte: a cell under pressure. Br J Rheumatol. 1994;33(10):901–8.PubMed
55.
Holmvall K, Camper L, Johansson S, Kimura JH, Lundgren-Akerlund E. Chondrocyte and chondrosarcoma cell integrins with affinity for collagen type II and their response to mechanical stress. Exp Cell Res. 1995;221(2):496–503.PubMed
56.
Vunjak-Novakovic G, Goldstein S. Biomechanical principles of cartilage and bone tissue engineering. Basic orthopaedic biomechanics and mechano-biology. Lippincott Williams and Wilkins; 2005.
57.
Lee C, Grad S, Wimmer M, Alini M. mechanical stimuli in articular cartilage tissue engineering. Topics in Tissue Engineering. 2006.
58.
Vanderploeg EJ, Wilson CG, Levenston ME. Articular chondrocytes derived from distinct tissue zones differentially respond to in vitro oscillatory tensile loading. Osteoarthr Cart. 2008;16(10):1228–36.
59.
Li Z, Yao S, Alini M, Grad S. Different response of articular chondrocyte subpopulations to surface motion. Osteoarthr Cart. 2007;15(9):1034–41.
60.
Grad S, Eglin D, Alini M, Stoddart MJ. Physical stimulation of chondrogenic cells in vitro: a review. Clin Orthop Relat Res. 2011;469(10):2764–72.PubMedCentralPubMed
61.
Unadkat HV, Hulsman M, Cornelissen K, Papenburg BJ, Truckenmuller RK, Carpenter AE, et al. An algorithm-based topographical biomaterials library to instruct cell fate. Proc Natl Acad Sci U S A. 2011;108(40):16565–70.PubMedCentralPubMed
62.•
Park S, Im GI. Stem cell responses to nanotopography. J Biomed Mater Res A. 2014. This review provides an overview of the effects of nanotopography on cell behavior in the context of musculoskeletal regeneration.
63.
64.
Discher DE, Janmey P, Wang YL. Tissue cells feel and respond to the stiffness of their substrate. Science. 2005;310(5751):1139–43.PubMed
65.
Janmey PA, Wells RG, Assoian RK, McCulloch CA. From tissue mechanics to transcription factors. Differentiation. 2013;86(3):112–20.PubMed
66.
Cigognini D, Lomas A, Kumar P, Satyam A, English A, Azeem A, et al. Engineering in vitro microenvironments for cell based therapies and drug discovery. Drug Discov Today. 2013;18(21–22):1099–108.PubMed
67.
Orsi G, Fagnano M, De Maria C, Montemurro F, Vozzi G. A new 3D concentration gradient maker and its application in building hydrogels with a 3D stiffness gradient. J Tissue Eng Regen Med. 2014.
68.
Schuh E, Hofmann S, Stok K, Notbohm H, Muller R, Rotter N. Chondrocyte redifferentiation in 3D: the effect of adhesion site density and substrate elasticity. J Biomed Mater Res A. 2012;100(1):38–47.PubMed
69.
Jiang F, Horber H, Howard J, Muller DJ. Assembly of collagen into microribbons: effects of pH and electrolytes. J Struct Biol. 2004;148(3):268–78.PubMed
70.
Little WC, Smith ML, Ebneter U, Vogel V. Assay to mechanically tune and optically probe fibrillar fibronectin conformations from fully relaxed to breakage. Matrix Biol. 2008;27(5):451–61.PubMed
71.
Smith ML, Gourdon D, Little WC, Kubow KE, Eguiluz RA, Luna-Morris S, et al. Force-induced unfolding of fibronectin in the extracellular matrix of living cells. PLoS Biol. 2007;5(10):e268.PubMedCentralPubMed
72.••
Lee J, Abdeen AA, Kilian KA. Rewiring mesenchymal stem cell lineage specification by switching the biophysical microenvironment. Sci Rep. 2014;4:5188. doi:10.​1038/​srep05188. This important new study demonstrates that MSCs remain susceptible to the biophysical properties of the extracellular matrix—even after several weeks of culture—and can redirect lineage specification in response to changes in the microenvironment.
73.
Liu C, Baek S, Kim J, Vasko E, Pyne R, Chan C. Effect of static pre-stretch induced surface anisotropy on orientation of mesenchymal stem cells. Cell Mol Bioeng. 2014;7(1):106–21.PubMedCentralPubMed
74.
Li Y, Chu JS, Kurpinski K, Li X, Bautista DM, Yang L, et al. Biophysical regulation of histone acetylation in mesenchymal stem cells. Biophys J. 2011;100(8):1902–9.PubMedCentralPubMed
75.
Wang N, Tytell JD, Ingber DE. Mechanotransduction at a distance: mechanically coupling the extracellular matrix with the nucleus. Nat Rev Mol Cell Biol. 2009;10(1):75–82.PubMed
76.
Gieni RS, Hendzel MJ. Mechanotransduction from the ECM to the genome: are the pieces now in place? J Cell Biochem. 2008;104(6):1964–87.PubMed
77.
Crisp M, Liu Q, Roux K, Rattner JB, Shanahan C, Burke B, et al. Coupling of the nucleus and cytoplasm: role of the LINC complex. J Cell Biol. 2006;172(1):41–53.PubMedCentralPubMed
78.
Steinmetz NJ, Bryant SJ. Chondroitin sulfate and dynamic loading alter chondrogenesis of human MSCs in PEG hydrogels. Biotechnol Bioeng. 2012;109(10):2671–82.PubMed
79.
Mhanna R, Kashyap A, Palazzolo G, Vallmajo-Martin Q, Becher J, Moller S, et al. Chondrocyte culture in three dimensional alginate sulfate hydrogels promotes proliferation while maintaining expression of chondrogenic markers. Tissue Eng A. 2014;20(9–10):1454–64.
80.
Govey PM, Loiselle AE, Donahue HJ. Biophysical regulation of stem cell differentiation. Curr Osteoporos Rep. 2013;11(2):83–91.PubMed
81.
Trappmann B, Chen CS. How cells sense extracellular matrix stiffness: a material’s perspective. Curr Opin Biotechnol. 2013;24(5):948–53.PubMedCentralPubMed
82.
Breuls RG, Jiya TU, Smit TH. Scaffold stiffness influences cell behavior: opportunities for skeletal tissue engineering. Open Orthop J. 2008;2:103–9.PubMedCentralPubMed
83.
Hing WA, Sherwin AF, Poole CA. The influence of the pericellular microenvironment on the chondrocyte response to osmotic challenge. Osteoarthr Cart. 2002;10(4):297–307.
84.
Likhitpanichkul M, Guo XE, Mow VC. The effect of matrix tension-compression nonlinearity and fixed negative charges on chondrocyte responses in cartilage. Mol Cell Biomech. 2005;2(4):191–204.PubMed
85.
Lai WM, Gu WY, Mow VC. On the conditional equivalence of chemical loading and mechanical loading on articular cartilage. J Biomech. 1998;31(12):1181–5.PubMed
86.
Schneiderman R, Keret D, Maroudas A. Effects of mechanical and osmotic pressure on the rate of glycosaminoglycan synthesis in the human adult femoral head cartilage: an in vitro study. J Orthop Res. 1986;4(4):393–408.PubMed
87.
Guilak F, Erickson GR, Ting-Beall HP. The effects of osmotic stress on the viscoelastic and physical properties of articular chondrocytes. Biophys J. 2002;82(2):720–7.PubMedCentralPubMed
88.
Cheung CY, Ko BC. NFAT5 in cellular adaptation to hypertonic stress—regulations and functional significance. J Mol Signal. 2013;8(1):5.PubMedCentralPubMed
89.
Jeon US, Kim JA, Sheen MR, Kwon HM. How tonicity regulates genes: story of TonEBP transcriptional activator. Acta Physiol (Oxf). 2006;187(1–2):241–7.
90.
Lee SD, Choi SY, Lim SW, Lamitina ST, Ho SN, Go WY, et al. TonEBP stimulates multiple cellular pathways for adaptation to hypertonic stress: organic osmolyte-dependent and -independent pathways. Am J Physiol Renal Physiol. 2011;300(3):F707–15.PubMedCentralPubMed
91.
Halterman JA, Kwon HM, Wamhoff BR. Tonicity-independent regulation of the osmosensitive transcription factor TonEBP (NFAT5). Am J Physiol Cell Physiol. 2012;302(1):C1–8.PubMedCentralPubMed
92.
van der Windt AE, Haak E, Das RH, Kops N, Welting TJ, Caron MM, et al. Physiological tonicity improves human chondrogenic marker expression through nuclear factor of activated T-cells 5 in vitro. Arthritis Res Ther. 2010;12(3):R100.PubMedCentralPubMed
93.
van der Windt AE, Haak E, Kops N, Verhaar JA, Weinans H, Jahr H. Inhibiting calcineurin activity under physiologic tonicity elevates anabolic but suppresses catabolic chondrocyte markers. Arthritis Rheum. 2012;64(6):1929–39.PubMed
94.
Koo J, Kim KI, Min BH, Lee GM. Controlling medium osmolality improves the expansion of human articular chondrocytes in serum-free media. Tissue Eng C Methods. 2010;16(5):957–63.
95.
Koo J, Kim KI, Min BH, Lee GM. Differential protein expression in human articular chondrocytes expanded in serum-free media of different medium osmolalities by DIGE. J Proteome Res. 2010;9(5):2480–7.PubMed
96.
Peffers MJ, Milner PI, Tew SR, Clegg PD. Regulation of SOX9 in normal and osteoarthritic equine articular chondrocytes by hyperosmotic loading. Osteoarthr Cart. 2010;18(11):1502–8.
97.
Tew SR, Peffers MJ, McKay TR, Lowe ET, Khan WS, Hardingham TE, et al. Hyperosmolarity regulates SOX9 mRNA posttranscriptionally in human articular chondrocytes. Am J Physiol Cell Physiol. 2009;297(4):C898–906.PubMedCentralPubMed
98.
Tsai TT, Danielson KG, Guttapalli A, Oguz E, Albert TJ, Shapiro IM, et al. TonEBP/OREBP is a regulator of nucleus pulposus cell function and survival in the intervertebral disc. J Biol Chem. 2006;281:25416–25424.
99.
Gajghate S, Hiyama A, Shah M, Sakai D, Anderson DG, Shapiro IM, et al. Osmolarity and intracellular calcium regulate aquaporin2 expression through TonEBP in nucleus pulposus cells of the intervertebral disc. J Bone Miner Res. 2009;24(6):992–1001.PubMedCentralPubMed
100.
Tsai TT, Guttapalli A, Agrawal A, Albert TJ, Shapiro IM, Risbud MV. MEK/ERK signaling controls osmoregulation of nucleus pulposus cells of the intervertebral disc by transactivation of TonEBP/OREBP. J Bone Miner Res. 2007;22(7):965–74.PubMed
101.
Pingguan-Murphy B, El-Azzeh M, Bader DL, Knight MM. Cyclic compression of chondrocytes modulates a purinergic calcium signalling pathway in a strain rate- and frequency-dependent manner. J Cell Physiol. 2006;209(2):389–97.PubMed
102.
Hiyama A, Gajghate S, Sakai D, Mochida J, Shapiro IM, Risbud MV. Activation of TonEBP by calcium controls {beta}1,3-glucuronosyltransferase-I expression, a key regulator of glycosaminoglycan synthesis in cells of the intervertebral disc. J Biol Chem. 2009;284(15):9824–34.PubMedCentralPubMed
103.
Erickson GR, Alexopoulos LG, Guilak F. Hyper-osmotic stress induces volume change and calcium transients in chondrocytes by transmembrane, phospholipid, and G-protein pathways. J Biomech. 2001;34(12):1527–35.PubMed
104.
Pritchard S, Votta BJ, Kumar S, Guilak F. Interleukin-1 inhibits osmotically induced calcium signaling and volume regulation in articular chondrocytes. Osteoarthr Cart. 2008;16(12):1466–73.
105.
Sanchez JC, Lopez-Zapata DF. Effects of osmotic challenges on membrane potential in human articular chondrocytes from healthy and osteoarthritic cartilage. Biorheology. 2010;47(5–6):321–31.PubMed
106.
Korhonen RK, Han SK, Herzog W. Osmotic loading of articular cartilage modulates cell deformations along primary collagen fibril directions. J Biomech. 2010;43(4):783–7.PubMed
107.
Finan JD, Chalut KJ, Wax A, Guilak F. Nonlinear osmotic properties of the cell nucleus. Ann Biomed Eng. 2009;37(3):477–91.PubMedCentralPubMed
108.
Szafranski JD, Grodzinsky AJ, Burger E, Gaschen V, Hung HH, Hunziker EB. Chondrocyte mechanotransduction: effects of compression on deformation of intracellular organelles and relevance to cellular biosynthesis. Osteoarthr Cart. 2004;12(12):937–46.
109.
Oswald ES, Chao PH, Bulinski JC, Ateshian GA, Hung CT. Dependence of zonal chondrocyte water transport properties on osmotic environment. Cell Mol Bioeng. 2008;1(4):339–48.PubMedCentralPubMed
110.
Xu X, Urban JP, Tirlapur UK, Cui Z. Osmolarity effects on bovine articular chondrocytes during three-dimensional culture in alginate beads. Osteoarthr Cart. 2010;18(3):433–9.
111.
Sun DD, Guo XE, Likhitpanichkul M, Lai WM, Mow VC. The influence of the fixed negative charges on mechanical and electrical behaviors of articular cartilage under unconfined compression. J Biomech Eng. 2004;126(1):6–16.PubMed
112.
Matta C, Mobasheri A, Gergely P, Zakany R. Ser/Thr-phosphoprotein phosphatases in chondrogenesis: neglected components of a two-player game. Cell Signal. 2014;26(10):2175–85.PubMed
113.
van der Windt AE, Jahr H, Farrell E, Verhaar JA, Weinans H, van Osch GJ. Calcineurin inhibitors promote chondrogenic marker expression of dedifferentiated human adult chondrocytes via stimulation of endogenous TGFbeta1 production. Tissue Eng A. 2010;16(1):1–10.
114.
Yoo SA, Park BH, Yoon HJ, Lee JY, Song JH, Kim HA, et al. Calcineurin modulates the catabolic and anabolic activity of chondrocytes and participates in the progression of experimental osteoarthritis. Arthritis Rheum. 2007;56(7):2299–311.PubMed
115.
Nakamura Y, Takarada T, Kodama A, Hinoi E, Yoneda Y. Predominant promotion by tacrolimus of chondrogenic differentiation to proliferating chondrocytes. J Pharmacol Sci. 2009;109(3):413–23.PubMed
116.
Reinhold MI, Abe M, Kapadia RM, Liao Z, Naski MC. FGF18 represses noggin expression and is induced by calcineurin. J Biol Chem. 2004;279(37):38209–19.PubMed
117.
Tomita M, Reinhold MI, Molkentin JD, Naski MC. Calcineurin and NFAT4 induce chondrogenesis. J Biol Chem. 2002;277(44):42214–8.PubMed
118.
Nishigaki F, Sakuma S, Ogawa T, Miyata S, Ohkubo T, Goto T. FK506 induces chondrogenic differentiation of clonal mouse embryonic carcinoma cells, ATDC5. Eur J Pharmacol. 2002;437(3):123–8.PubMed
119.
Obayashi K, Tomonari M, Yoshimatsu H, Fukuyama R, Ieiri I, Higuchi S, et al. Dosing time-dependency of the arthritis-inhibiting effect of tacrolimus in mice. J Pharmacol Sci. 2011;116(3):264–73.PubMed
120.
Kang KY, Ju JH, Song YW, Yoo DH, Kim HY, Park SH. Tacrolimus treatment increases bone formation in patients with rheumatoid arthritis. Rheumatol Int. 2013;33(8):2159–63.PubMed
121.
Crabtree GR. Calcium, calcineurin, and the control of transcription. J Biol Chem. 2001;276(4):2313–6.PubMed
122.
Wu H, Peisley A, Graef IA, Crabtree GR. NFAT signaling and the invention of vertebrates. Trends Cell Biol. 2007;17(6):251–60.PubMed
123.
Ranger AM, Gerstenfeld LC, Wang J, Kon T, Bae H, Gravallese EM, et al. The nuclear factor of activated T cells (NFAT) transcription factor NFATp (NFATc2) is a repressor of chondrogenesis. J Exp Med. 2000;191(1):9–22.PubMedCentralPubMed
124.
Wang J, Gardner BM, Lu Q, Rodova M, Woodbury BG, Yost JG, et al. Transcription factor Nfat1 deficiency causes osteoarthritis through dysfunction of adult articular chondrocytes. J Pathol. 2009;219(2):163–72.PubMedCentralPubMed
125.
Greenblatt MB, Ritter SY, Wright J, Tsang K, Hu D, Glimcher LH, et al. NFATc1 and NFATc2 repress spontaneous osteoarthritis. Proc Natl Acad Sci U S A. 2013;110(49):19914–9.PubMedCentralPubMed
126.
Sitara D, Aliprantis AO. Transcriptional regulation of bone and joint remodeling by NFAT. Immunol Rev. 2010;233(1):286–300.PubMedCentralPubMed
127.
Yaykasli KO, Oohashi T, Hirohata S, Hatipoglu OF, Inagawa K, Demircan K, et al. ADAMTS9 activation by interleukin 1 beta via NFATc1 in OUMS-27 chondrosarcoma cells and in human chondrocytes. Mol Cell Biochem. 2009;323(1–2):69–79.PubMed
128.
Thirunavukkarasu K, Pei Y, Moore TL, Wang H, Yu XP, Geiser AG, et al. Regulation of the human ADAMTS-4 promoter by transcription factors and cytokines. Biochem Biophys Res Commun. 2006;345(1):197–204.PubMed
129.
Rodova M, Lu Q, Li Y, Woodbury BG, Crist JD, Gardner BM, et al. Nfat1 regulates adult articular chondrocyte function through its age-dependent expression mediated by epigenetic histone methylation. J Bone Miner Res. 2011;26(8):1974–86.PubMedCentralPubMed
130.••
Lin SS, Tzeng BH, Lee KR, Smith RJ, Campbell KP, Chen CC. Cav3.2 T-type calcium channel is required for the NFAT-dependent Sox9 expression in tracheal cartilage. Proc Natl Acad Sci U S A. 2014;111(19):E1990–8. This recent study links ion channel function to the chondrocyte phenotype by demonstrating that calcium influx via the Cav3.2 T-type calcium channel regulates Sox9 expression through the calcineurin/NFAT signaling pathway during chondrogenesis in tracheal cartilage.PubMedCentralPubMed
131.
Matta C, Fodor J, Szijgyarto Z, Juhasz T, Gergely P, Csernoch L, et al. Cytosolic free Ca2+ concentration exhibits a characteristic temporal pattern during in vitro cartilage differentiation: a possible regulatory role of calcineurin in Ca-signalling of chondrogenic cells. Cell Calcium. 2008;44(3):310–23. doi:10.​1016/​j.​ceca.​2007.​12.​010.PubMed
132.
Miclea RL, Siebelt M, Finos L, Goeman JJ, Lowik CW, Oostdijk W, et al. Inhibition of Gsk3beta in cartilage induces osteoarthritic features through activation of the canonical Wnt signaling pathway. Osteoarthr Cart. 2011;19(11):1363–72.
133.
Siebelt M, van der Windt AE, Groen HC, Sandker M, Waarsing JH, Muller C, et al. FK506 protects against articular cartilage collagenous extra-cellular matrix degradation. Osteoarthr Cart. 2014;22(4):591–600.
134.
Zanotti S, Canalis E. Notch suppresses nuclear factor of activated T cells (NFAT) transactivation and Nfatc1 expression in chondrocytes. Endocrinology. 2013;154(2):762–72.PubMedCentralPubMed
135.
Bradley EW, Drissi MH. WNT5A regulates chondrocyte differentiation through differential use of the CaN/NFAT and IKK/NF-kappaB pathways. Mol Endocrinol. 2010;24(8):1581–93.PubMed
136.
Pitsillides AA, Beier F. Cartilage biology in osteoarthritis—lessons from developmental biology. Nat Rev Rheumatol. 2011;7(11):654–63.PubMed
137.
Roddy KA, Prendergast PJ, Murphy P. Mechanical influences on morphogenesis of the knee joint revealed through morphological, molecular and computational analysis of immobilised embryos. PLoS One. 2011;6(2):e17526.PubMedCentralPubMed
138.
Sarraf CE, Otto WR, Eastwood M. In vitro mesenchymal stem cell differentiation after mechanical stimulation. Cell Prolif. 2011;44(1):99–108.PubMed
139.
Sun HB. Mechanical loading, cartilage degradation, and arthritis. Ann N Y Acad Sci. 2010;1211:37–50.PubMed
140.•
O’Conor CJ, Case N, Guilak F. Mechanical regulation of chondrogenesis. Stem Cell Res Ther. 2013;4(4):61. This recent review article summarizes some of the latest findings on mechanically stimulated chondrogenesis, highlighting the effects of mechanical stimulation on matrix maintenance and terminal differentiation, as well as the use of multifactorial bioreactors.PubMedCentralPubMed
141.
Muhammad H, Rais Y, Miosge N, Ornan EM. The primary cilium as a dual sensor of mechanochemical signals in chondrocytes. Cell Mol Life Sci. 2012;69(13):2101–7.PubMedCentralPubMed
142.
Wang Y, Maciejewski BS, Lee N, Silbert O, McKnight NL, Frangos JA, et al. Strain-induced fetal type II epithelial cell differentiation is mediated via cAMP-PKA-dependent signaling pathway. Am J Physiol Lung Cell Mol Physiol. 2006;291(4):L820–7.PubMed
143.
Lee T, Kim SJ, Sumpio BE. Role of PP2A in the regulation of p38 MAPK activation in bovine aortic endothelial cells exposed to cyclic strain. J Cell Physiol. 2003;194(3):349–55.PubMed
144.
Juhász T, Matta C, Somogyi C, Katona É, Takács R, Soha RF, et al. Mechanical loading stimulates chondrogenesis via the PKA/CREB-Sox9 and PP2A pathways in chicken micromass cultures. Cell Signal. 2014;26(3):468–82. doi:10.​1016/​j.​cellsig.​2013.​12.​001
145.
Zakany R, Szucs K, Bako E, Felszeghy S, Czifra G, Biro T, et al. Protein phosphatase 2A is involved in the regulation of protein kinase A signaling pathway during in vitro chondrogenesis. Exp Cell Res. 2002;275(1):1–8.PubMed
146.
Yoon YM, Kim SJ, Oh CD, Ju JW, Song WK, Yoo YJ, et al. Maintenance of differentiated phenotype of articular chondrocytes by protein kinase C and extracellular signal-regulated protein kinase. J Biol Chem. 2002;277(10):8412–20.PubMed
147.
Lee YA, Kang SS, Baek SH, Jung JC, Jin EJ, Tak EN, et al. Redifferentiation of dedifferentiated chondrocytes on chitosan membranes and involvement of PKCalpha and P38 MAP kinase. Mol Cells. 2007;24(1):9–15.PubMed
148.
Kawanishi M, Oura A, Furukawa K, Fukubayashi T, Nakamura K, Tateishi T, et al. Redifferentiation of dedifferentiated bovine articular chondrocytes enhanced by cyclic hydrostatic pressure under a gas-controlled system. Tissue Eng. 2007;13(5):957–64.PubMed
149.
Matta C, Zakany R. Calcium signalling in chondrogenesis: implications for cartilage repair. Front Biosci (Schol Ed). 2013;5:305–24.
150.
Mobasheri A, Lewis R, Maxwell JE, Hill C, Womack M, Barrett-Jolley R. Characterization of a stretch-activated potassium channel in chondrocytes. J Cell Physiol. 2010;223(2):511–8.PubMedCentralPubMed
150.••
O’Conor CJ, Leddy HA, Benefield HC, Liedtke WB, Guilak F. TRPV4-mediated mechanotransduction regulates the metabolic response of chondrocytes to dynamic loading. Proc Natl Acad Sci U S A. 2014;111(4):1316–21. In this paper, the authors demonstrate that TRPV4, a calcium-permeable, nonselective cation channel, is directly involved in regulating metabolic responses of chondrocytes to dynamic load.PubMedCentralPubMed
152.
Roberts SR, Knight MM, Lee DA, Bader DL. Mechanical compression influences intracellular Ca2+ signaling in chondrocytes seeded in agarose constructs. J Appl Physiol (1985). 2001;90(4):1385–91.
153.
Wilsman NJ. Cilia of adult canine articular chondrocytes. J Ultrastruct Res. 1978;64(3):270–81.PubMed
154.
Wann AK, Zuo N, Haycraft CJ, Jensen CG, Poole CA, McGlashan SR, et al. Primary cilia mediate mechanotransduction through control of ATP-induced Ca2+ signaling in compressed chondrocytes. Faseb J. 2012;26(4):1663–71.PubMedCentralPubMed
Metadata
Title
Physicochemical and Biomechanical Stimuli in Cell-Based Articular Cartilage Repair
Authors
Holger Jahr
Csaba Matta
Ali Mobasheri
Publication date
01-03-2015
Publisher
Springer US
Published in
Current Rheumatology Reports / Issue 3/2015
Print ISSN: 1523-3774
Electronic ISSN: 1534-6307
DOI
https://doi.org/10.1007/s11926-014-0493-9

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