Skip to main content
Top
Published in: Journal of Orthopaedic Surgery and Research 1/2018

Open Access 01-12-2018 | Research article

Roles and mechanisms of leptin in osteogenic stimulation in cervical ossification of the posterior longitudinal ligament

Authors: Bin Feng, Shiliang Cao, Jiliang Zhai, Yi Ren, Jianhua Hu, Ye Tian, Xisheng Weng

Published in: Journal of Orthopaedic Surgery and Research | Issue 1/2018

Login to get access

Abstract

Background

Hyperleptinemia is a common feature of obese people, and leptin, an adipocyte-derived cytokine, is believed to be an important factor in the pathogenesis of cervical ossification of the posterior longitudinal ligament(C-OPLL). So this research was to identify the relation between the serum leptin and bone metabolic markers and how the leptin induced osteogenic effect in C-OPLL.

Methods

Sixty-four samples were selected to determine the concentration of leptin, insulin, and alkaline phosphatase. And the association of leptin with these factors was also examined. We also evaluate the effect of leptin on the development of C-OPLL and further explored the possible underlying mechanism in vitro.

Results

We found that serum leptin concentrations were higher in females than in males. Serum leptin and ALP concentrations were increased significantly in C-OPLL females compared to non-OPLL females. In OPLL subjects, the serum leptin concentration corrected for body mass index correlated negatively with the ALP concentrations. In C-OPLL cells, leptin treatment led to a significant increase in mRNA expressions of ALP and OCN and formation of mineralized nodule. Our experiments reported here that osteogenic effect of leptin in C-OPLL cells could be mediated via ERK1/2, p38 MAPK, and/or JNK signaling pathways.

Conclusions

From this research, we got that leptin treatment led to a significant increase in mRNA expressions of ALP and OCN and formation of mineralized nodule. And the osteogenic effect of leptin in C-OPLL cells could be mediated via ERK1/2, p38 MAPK, and/or JNK signaling pathways.
Literature
1.
go back to reference Chen Y, Wang X, Yang H, et al. Upregulated expression of PERK in spinal ligament fibroblasts from the patients with ossification of the posterior longitudinal ligament. Eur Spine J. 2014;23:447–54.CrossRefPubMed Chen Y, Wang X, Yang H, et al. Upregulated expression of PERK in spinal ligament fibroblasts from the patients with ossification of the posterior longitudinal ligament. Eur Spine J. 2014;23:447–54.CrossRefPubMed
2.
go back to reference Shi L, Cai G, Shi J, et al. Ossification of the posterior ligament is mediated by osterix via inhibition of the beta-catenin signaling pathway. Exp Cell Res. 2016;349:53–9.CrossRefPubMed Shi L, Cai G, Shi J, et al. Ossification of the posterior ligament is mediated by osterix via inhibition of the beta-catenin signaling pathway. Exp Cell Res. 2016;349:53–9.CrossRefPubMed
3.
go back to reference Matsunaga S, Kukita M, Hayashi K, et al. Pathogenesis of myelopathy in patients with ossification of the posterior longitudinal ligament. J Neurosurg. 2002;96:168–72.PubMed Matsunaga S, Kukita M, Hayashi K, et al. Pathogenesis of myelopathy in patients with ossification of the posterior longitudinal ligament. J Neurosurg. 2002;96:168–72.PubMed
4.
go back to reference Kawaguchi Y, Nakano M, Yasuda T, et al. Serum biomarkers in patients with ossification of the posterior longitudinal ligament (OPLL): inflammation in OPLL. PLoS One. 2017;12:e0174881.CrossRefPubMedPubMedCentral Kawaguchi Y, Nakano M, Yasuda T, et al. Serum biomarkers in patients with ossification of the posterior longitudinal ligament (OPLL): inflammation in OPLL. PLoS One. 2017;12:e0174881.CrossRefPubMedPubMedCentral
5.
go back to reference Nakajima M, Takahashi A, Tsuji T, et al. A genome-wide association study identifies susceptibility loci for ossification of the posterior longitudinal ligament of the spine. Nat Genet. 2014;46:1012–6.CrossRefPubMed Nakajima M, Takahashi A, Tsuji T, et al. A genome-wide association study identifies susceptibility loci for ossification of the posterior longitudinal ligament of the spine. Nat Genet. 2014;46:1012–6.CrossRefPubMed
6.
go back to reference Nakajima M, Kou I, Ohashi H, et al. Identification and functional characterization of RSPO2 as a susceptibility gene for ossification of the posterior longitudinal ligament of the spine. Am J Hum Genet. 2016;99:202–7.CrossRefPubMedPubMedCentral Nakajima M, Kou I, Ohashi H, et al. Identification and functional characterization of RSPO2 as a susceptibility gene for ossification of the posterior longitudinal ligament of the spine. Am J Hum Genet. 2016;99:202–7.CrossRefPubMedPubMedCentral
7.
go back to reference Tanaka T, Ikari K, Furushima K, et al. Genomewide linkage and linkage disequilibrium analyses identify COL6A1, on chromosome 21, as the locus for ossification of the posterior longitudinal ligament of the spine. Am J Hum Genet. 2003;73:812–22.CrossRefPubMedPubMedCentral Tanaka T, Ikari K, Furushima K, et al. Genomewide linkage and linkage disequilibrium analyses identify COL6A1, on chromosome 21, as the locus for ossification of the posterior longitudinal ligament of the spine. Am J Hum Genet. 2003;73:812–22.CrossRefPubMedPubMedCentral
8.
go back to reference Tsuyama N. Ossification of the posterior longitudinal ligament of the spine. Clin Orthop Relat Res. 1984;(184):71–84. Tsuyama N. Ossification of the posterior longitudinal ligament of the spine. Clin Orthop Relat Res. 1984;(184):71–84.
9.
go back to reference Jiang H, Chen Y, Chen G, et al. Leptin accelerates the pathogenesis of heterotopic ossification in rat tendon tissues via mTORC1 signaling. J Cell Physiol. 2018;233(2):1017–28. Jiang H, Chen Y, Chen G, et al. Leptin accelerates the pathogenesis of heterotopic ossification in rat tendon tissues via mTORC1 signaling. J Cell Physiol. 2018;233(2):1017–28.
10.
go back to reference Philbrick KA, Wong CP, Branscum AJ, et al. Leptin stimulates bone formation in ob/ob mice at doses having minimal impact on energy metabolism. J Endocrinol. 2017;232:461–74.CrossRefPubMedPubMedCentral Philbrick KA, Wong CP, Branscum AJ, et al. Leptin stimulates bone formation in ob/ob mice at doses having minimal impact on energy metabolism. J Endocrinol. 2017;232:461–74.CrossRefPubMedPubMedCentral
11.
go back to reference Fan D, Chen Z, Chen Y, et al. Mechanistic roles of leptin in osteogenic stimulation in thoracic ligament flavum cells. J Biol Chem. 2007;282:29958–66.CrossRefPubMed Fan D, Chen Z, Chen Y, et al. Mechanistic roles of leptin in osteogenic stimulation in thoracic ligament flavum cells. J Biol Chem. 2007;282:29958–66.CrossRefPubMed
12.
go back to reference Zheng B, Jiang J, Luo K, et al. Increased osteogenesis in osteoporotic bone marrow stromal cells by overexpression of leptin. Cell Tissue Res. 2015;361:845–56.CrossRefPubMed Zheng B, Jiang J, Luo K, et al. Increased osteogenesis in osteoporotic bone marrow stromal cells by overexpression of leptin. Cell Tissue Res. 2015;361:845–56.CrossRefPubMed
13.
go back to reference Lamghari M, Tavares L, Camboa N, et al. Leptin effect on RANKL and OPG expression in MC3T3-E1 osteoblasts. J Cell Biochem. 2006;98:1123–9.CrossRefPubMed Lamghari M, Tavares L, Camboa N, et al. Leptin effect on RANKL and OPG expression in MC3T3-E1 osteoblasts. J Cell Biochem. 2006;98:1123–9.CrossRefPubMed
15.
go back to reference Steppan CM, Crawford DT, Chidsey-Frink KL, et al. Leptin is a potent stimulator of bone growth in ob/ob mice. Regul Pept. 2000;92:73–8.CrossRefPubMed Steppan CM, Crawford DT, Chidsey-Frink KL, et al. Leptin is a potent stimulator of bone growth in ob/ob mice. Regul Pept. 2000;92:73–8.CrossRefPubMed
16.
go back to reference Ducy P, Amling M, Takeda S, et al. Leptin inhibits bone formation through a hypothalamic relay: a central control of bone mass. Cell. 2000;100:197–207.CrossRefPubMed Ducy P, Amling M, Takeda S, et al. Leptin inhibits bone formation through a hypothalamic relay: a central control of bone mass. Cell. 2000;100:197–207.CrossRefPubMed
17.
go back to reference Ikeda Y, Nakajima A, Aiba A, et al. Association between serum leptin and bone metabolic markers, and the development of heterotopic ossification of the spinal ligament in female patients with ossification of the posterior longitudinal ligament. Eur Spine J. 2011;20:1450–8.CrossRefPubMedPubMedCentral Ikeda Y, Nakajima A, Aiba A, et al. Association between serum leptin and bone metabolic markers, and the development of heterotopic ossification of the spinal ligament in female patients with ossification of the posterior longitudinal ligament. Eur Spine J. 2011;20:1450–8.CrossRefPubMedPubMedCentral
18.
go back to reference Shirakura Y, Sugiyama T, Tanaka H, et al. Hyperleptinemia in female patients with ossification of spinal ligaments. Biochem Biophys Res Commun. 2000;267:752–5.CrossRefPubMed Shirakura Y, Sugiyama T, Tanaka H, et al. Hyperleptinemia in female patients with ossification of spinal ligaments. Biochem Biophys Res Commun. 2000;267:752–5.CrossRefPubMed
19.
go back to reference Scotece M, Mobasheri A. Leptin in osteoarthritis: focus on articular cartilage and chondrocytes. Life Sci. 2015;140:75–8.CrossRefPubMed Scotece M, Mobasheri A. Leptin in osteoarthritis: focus on articular cartilage and chondrocytes. Life Sci. 2015;140:75–8.CrossRefPubMed
20.
go back to reference Upadhyay J, Farr OM, Mantzoros CS. The role of leptin in regulating bone metabolism. Metabolism. 2015;64:105–13.CrossRefPubMed Upadhyay J, Farr OM, Mantzoros CS. The role of leptin in regulating bone metabolism. Metabolism. 2015;64:105–13.CrossRefPubMed
21.
go back to reference Vuolteenaho K, Koskinen A, Moilanen E. Leptin—a link between obesity and osteoarthritis. Applications for prevention and treatment. Basic Clin Pharmacol Toxicol. 2014;114:103–8.CrossRefPubMed Vuolteenaho K, Koskinen A, Moilanen E. Leptin—a link between obesity and osteoarthritis. Applications for prevention and treatment. Basic Clin Pharmacol Toxicol. 2014;114:103–8.CrossRefPubMed
22.
go back to reference Shingyouchi Y, Nagahama A, Niida M. Ligamentous ossification of the cervical spine in the late middle-aged Japanese men. Its relation to body mass index and glucose metabolism. Spine. 1996;21:2474–8.CrossRefPubMed Shingyouchi Y, Nagahama A, Niida M. Ligamentous ossification of the cervical spine in the late middle-aged Japanese men. Its relation to body mass index and glucose metabolism. Spine. 1996;21:2474–8.CrossRefPubMed
24.
go back to reference Akune T, Ogata N, Seichi A, et al. Insulin secretory response is positively associated with the extent of ossification of the posterior longitudinal ligament of the spine. J Bone Joint Surg. 2001;83a:1537–44.CrossRef Akune T, Ogata N, Seichi A, et al. Insulin secretory response is positively associated with the extent of ossification of the posterior longitudinal ligament of the spine. J Bone Joint Surg. 2001;83a:1537–44.CrossRef
25.
go back to reference Dagogo-Jack S, Fanelli C, Paramore D, et al. Plasma leptin and insulin relationships in obese and nonobese humans. Diabetes. 1996;45:695–8.CrossRefPubMed Dagogo-Jack S, Fanelli C, Paramore D, et al. Plasma leptin and insulin relationships in obese and nonobese humans. Diabetes. 1996;45:695–8.CrossRefPubMed
26.
go back to reference Cornish J, Callon K, Bava U, et al. Leptin directly regulates bone cell function in vitro and reduces bone fragility in vivo. J Endocrinol. 2002;175:405–15.CrossRefPubMed Cornish J, Callon K, Bava U, et al. Leptin directly regulates bone cell function in vitro and reduces bone fragility in vivo. J Endocrinol. 2002;175:405–15.CrossRefPubMed
27.
go back to reference Zheng B, Jiang J, Chen Y, et al. Leptin overexpression in bone marrow stromal cells promotes periodontal regeneration in a rat model of osteoporosis. J Periodontol. 2017;88:808–18.CrossRefPubMed Zheng B, Jiang J, Chen Y, et al. Leptin overexpression in bone marrow stromal cells promotes periodontal regeneration in a rat model of osteoporosis. J Periodontol. 2017;88:808–18.CrossRefPubMed
28.
go back to reference Turner RT, Kalra SP, Wong CP, et al. Peripheral leptin regulates bone formation. J Bone Miner Res Off J Am Soc Bone Miner Res. 2013;28:22–34.CrossRef Turner RT, Kalra SP, Wong CP, et al. Peripheral leptin regulates bone formation. J Bone Miner Res Off J Am Soc Bone Miner Res. 2013;28:22–34.CrossRef
29.
go back to reference Ben-Eliezer M, Phillip M, Gat-Yablonski G. Leptin regulates chondrogenic differentiation in ATDC5 cell-line through JAK/STAT and MAPK pathways. Endocrine. 2007;32:235–44.CrossRefPubMed Ben-Eliezer M, Phillip M, Gat-Yablonski G. Leptin regulates chondrogenic differentiation in ATDC5 cell-line through JAK/STAT and MAPK pathways. Endocrine. 2007;32:235–44.CrossRefPubMed
30.
go back to reference Nepal M, Li L, Cho HK, et al. Kaempferol induces chondrogenesis in ATDC5 cells through activation of ERK/BMP-2 signaling pathway. Food Chem Toxicol. 2013;62:238–45.CrossRefPubMed Nepal M, Li L, Cho HK, et al. Kaempferol induces chondrogenesis in ATDC5 cells through activation of ERK/BMP-2 signaling pathway. Food Chem Toxicol. 2013;62:238–45.CrossRefPubMed
31.
go back to reference Oh HK, Choi YS, Yang YI, et al. Leptin receptor is induced in endometriosis and leptin stimulates the growth of endometriotic epithelial cells through the JAK2/STAT3 and ERK pathways. Mol Hum Reprod. 2013;19:160–8.CrossRefPubMed Oh HK, Choi YS, Yang YI, et al. Leptin receptor is induced in endometriosis and leptin stimulates the growth of endometriotic epithelial cells through the JAK2/STAT3 and ERK pathways. Mol Hum Reprod. 2013;19:160–8.CrossRefPubMed
32.
go back to reference Ohba S, Lanigan TM, Roessler BJ. Leptin receptor JAK2/STAT3 signaling modulates expression of Frizzled receptors in articular chondrocytes. Osteoarthr Cartil. 2010;18:1620–9.CrossRefPubMedPubMedCentral Ohba S, Lanigan TM, Roessler BJ. Leptin receptor JAK2/STAT3 signaling modulates expression of Frizzled receptors in articular chondrocytes. Osteoarthr Cartil. 2010;18:1620–9.CrossRefPubMedPubMedCentral
33.
go back to reference Otero M, Lago R, Gómez R, et al. Phosphatidylinositol 3-kinase, MEK-1 and p38 mediate leptin/interferon-gamma synergistic NOS type II induction in chondrocytes. Life Sci. 2007;81:1452–60.CrossRefPubMed Otero M, Lago R, Gómez R, et al. Phosphatidylinositol 3-kinase, MEK-1 and p38 mediate leptin/interferon-gamma synergistic NOS type II induction in chondrocytes. Life Sci. 2007;81:1452–60.CrossRefPubMed
34.
go back to reference Chen XX, Yang T. Roles of leptin in bone metabolism and bone diseases. J Bone Miner Metab. 2015;33:474–85.CrossRefPubMed Chen XX, Yang T. Roles of leptin in bone metabolism and bone diseases. J Bone Miner Metab. 2015;33:474–85.CrossRefPubMed
Metadata
Title
Roles and mechanisms of leptin in osteogenic stimulation in cervical ossification of the posterior longitudinal ligament
Authors
Bin Feng
Shiliang Cao
Jiliang Zhai
Yi Ren
Jianhua Hu
Ye Tian
Xisheng Weng
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Journal of Orthopaedic Surgery and Research / Issue 1/2018
Electronic ISSN: 1749-799X
DOI
https://doi.org/10.1186/s13018-018-0864-4

Other articles of this Issue 1/2018

Journal of Orthopaedic Surgery and Research 1/2018 Go to the issue