Research progress on the role of adipokines in intervertebral disc degeneration_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

GONG Chaoyang , ZHAO Guanghai , XIANG Gao , LIU Kaixin ,  ZHANG Haihong

Department of Orthopedics, Lanzhou University Second Hospital, Gansu Key Laboratory of Bone and Joint Diseases, Lanzhou Gansu, 730000, P.R.China;

Corresponding author：

ZHANG Haihong, Email: zhanghaihong1968@sina.com

Keywords：

Adipokine; intervertebral disc degeneration; inflammatory response; biotherapy

DOI：

10.7507/1002-1892.201906004

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

Objective To review the research progress of the role and mechanism of adipokines in intervertebral disc degeneration (IVDD) in recent years.Methods The domestic and foreign literature related to adipokines in the process of IVDD was extensively reviewed. The types and functions of adipokines, the role and mechanism in the process of IVDD, and the application prospects of intervertebral disc biotherapy were reviewed.Results As a kind of bioactive substance secreted by adipose tissue, adipokine plays an important role in bone and joint diseases, metabolic diseases, and breast cancer. During IVDD, most adipokines can activate multiple signaling pathways by binding to autoreceptors, cause the proliferation and apoptosis of cells and proinflammatory and anti-inflammatory factors parasecretions in the intervertebral disc, and lead to imbalance of intradiscal metabolism and establishment of the initial inflammatory environment, and finally cause the IVDD.Conclusion Adipokines, as a biologically active substance with metabolic and immunomodulatory functions, play important roles in the occurrence, development, and biological treatment of IVDD.

Citation： GONG Chaoyang, ZHAO Guanghai, XIANG Gao, LIU Kaixin, ZHANG Haihong. Research progress on the role of adipokines in intervertebral disc degeneration. Chinese Journal of Reparative and Reconstructive Surgery, 2020, 34(3): 399-403. doi: 10.7507/1002-1892.201906004 Copy

1.	Sampara P, Banala RR, Vemuri SK, et al. Understanding the molecular biology of intervertebral disc degeneration and potential gene therapy strategies for regeneration: a review. Gene Ther, 2018, 25(2): 67-82.
2.	Kadow T, Sowa G, Vo N, et al. Molecular basis of intervertebral disc degeneration and herniations: what are the important translational questions? Clin Orthop Relat Res, 2015, 473(6): 1903-1912.
3.	侯孝忠, 徐林飞, 易威威, 等. 内质网应激对吸烟诱导的髓核细胞凋亡与炎性反应的影响研究. 中国修复重建外科杂志, 2019, 33(6): 736-742.
4.	陈琪, 石芳芳, 杨曦, 等. 不同代次髓核细胞生物学特性的比较研究. 中国修复重建外科杂志, 2018, 32(6): 660-667.
5.	MacDonald IJ, Liu SC, Huang CC, et al. Associations between adipokines in arthritic disease and implications for obesity. Int J Mol Sci, 2019, 20(6): pii: E1505.
6.	Ruiz-Fernández C, Francisco V, Pino J, et al. Molecular relationships among obesity, inflammation and intervertebral disc degeneration: are adipokines the common link? Int J Mol Sci, 2019, 20(8): pii: E2030.
7.	Fasshauer M, Blüher M. Adipokines in health and disease. Trends Pharmacol Sci, 2015, 36(7): 461-470.
8.	Gandhi R, Sharma A, Kapoor M, et al. Racial differences in serum adipokine and insulin levels in a matched osteoarthritis sample: a pilot study. J Obes, 2016, 2016: 8746268.
9.	Ouchi N, Parker JL, Lugus JJ, et al. Adipokines in inflammation and metabolic disease. Nat Rev Immunol, 2011, 11(2): 85-97.
10.	Dowdell J, Erwin M, Choma T, et al. Intervertebral disk degeneration and repair. Neurosurgery, 2017, 80(3S): S46-S54.
11.	Segar AH, Fairbank JCT, Urban J. Leptin and the intervertebral disc: a biochemical link exists between obesity, intervertebral disc degeneration and low back pain-an in vitro study in a bovine model. Eur Spine J, 2019, 28(2): 214-223.
12.	Francisco V, Pino J, Campos-Cabaleiro V, et al. Obesity, fat mass and immune system: role for leptin. Front Physiol, 2018, 9: 640.
13.	Zhao CQ, Liu D, Li H, et al. Expression of leptin and its functional receptor on disc cells: contribution to cell proliferation. Spine (Phila Pa 1976), 2008, 33(23): E858-E864.
14.	Li Z, Shen J, Wu WK, et al. Leptin induces cyclin D1 expression and proliferation of human nucleus pulposus cells via JAK/STAT, PI3K/Akt and MEK/ERK pathways. PLoS One, 2012, 7(12): e53176.
15.	Li Z, Yu X, Liang J, et al. Leptin downregulates aggrecan through the p38-ADAMST pathway in human nucleus pulposus cells. PLoS One, 2014, 9(10): e109595.
16.	Han YC, Ma B, Guo S, et al. Leptin regulates disc cartilage endplate degeneration and ossification through activation of the MAPK-ERK signalling pathway in vivo and in vitro. J Cell Mol Med, 2018, 22(4): 2098-2109.
17.	Liu M, Liu F. Regulation of adiponectin multimerization, signaling and function. Best Pract Res Clin Endocrinol Metab, 2014, 28(1): 25-31.
18.	Yamauchi T, Iwabu M, Okada-Iwabu M, et al. Adiponectin receptors: a review of their structure, function and how they work. Best Pract Res Clin Endocrinol Metab, 2014, 28(1): 15-23.
19.	Yuan B, Huang L, Yan M, et al. Adiponectin downregulates TNF-α expression in degenerated intervertebral discs. Spine (Phila Pa 1976), 2018, 43(7): E381-E389.
20.	Terashima Y, Kakutani K, Yurube T, et al. Expression of adiponectin receptors in human and rat intervertebral disc cells and changes in receptor expression during disc degeneration using a rat tail temporary static compression model. J Orthop Surg Res, 2016, 11(1): 147.
21.	Jamaluddin MS, Weakley SM, Yao Q, et al. Resistin: functional roles and therapeutic considerations for cardiovascular disease. Br J Pharmacol, 2012, 165(3): 622-632.
22.	Fang WQ, Zhang Q, Peng YB, et al. Resistin level is positively correlated with thrombotic complications in Southern Chinese metabolic syndrome patients. J Endocrinol Invest, 2011, 34(2): e36-e42.
23.	Li Z, Wang X, Pan H, et al. Resistin promotes CCL4 expression through toll-like receptor-4 and activation of the p38-MAPK and NF-κB signaling pathways: implications for intervertebral disc degeneration. Osteoarthritis Cartilage, 2017, 25(2): 341-350.
24.	Liu C, Yang H, Gao F, et al. Resistin Promotes Intervertebral Disc Degeneration by Upregulation of ADAMTS-5 Through p38 MAPK Signaling Pathway. Spine (Phila Pa 1976), 2016, 41(18): 1414-1420.
25.	Wei J, Hettinghouse A, Liu C. The role of progranulin in arthritis. Ann N Y Acad Sci, 2016, 1383(1): 5-20.
26.	Zhao YP, Tian QY, Liu B, et al. Progranulin knockout accelerates intervertebral disc degeneration in aging mice. Sci Rep, 2015, 5: 9102.
27.	Wang S, Wei J, Fan Y, et al. Progranulin is positively associated with intervertebral disc degeneration by interaction with IL-10 and IL-17 through TNF pathways. Inflammation, 2018, 41(5): 1852-1863.
28.	Francisco V, Pérez T, Pino J, et al. Biomechanics, obesity, and osteoarthritis. The role of adipokines: When the levee breaks. J Orthop Res, 2018, 36(2): 594-604.
29.	Radzicka S, Pietryga M, Iciek R, et al. The role of visfatin in pathogenesis of gestational diabetes (GDM). Ginekol Pol, 2018, 89(9): 518-521.
30.	Shi C, Wu H, Du D, et al. Nicotinamide phosphoribosyltransferase inhibitor APO866 prevents IL-1β-induced human nucleus pulposus cell degeneration via autophagy. Cell Physiol Biochem, 2018, 49(6): 2463-2482.
31.	Colldén G, Tschöp MH, Müller TD. Therapeutic potential of targeting the ghrelin pathway. Int J Mol Sci, 2017, 18(4): pii: E798.
32.	Pereira JADS, da Silva FC, de Moraes-Vieira PMM. The impact of ghrelin in metabolic diseases: an immune perspective. J Diabetes Res, 2017, 2017: 4527980.
33.	Li W, Wu X, Qu R, et al. Ghrelin protects against nucleus pulposus degeneration through inhibition of NF-κB signaling pathway and activation of Akt signaling pathway. Oncotarget, 2017, 8(54): 91887-91901.
34.	Francisco V, Pino J, Gonzalez-Gay MA, et al. Adipokines and inflammation: is it a question of weight? Br J Pharmacol, 2018, 175(10): 1569-1579.
35.	Kao TH, Peng YJ, Salter DM, et al. Nerve growth factor increases MMP9 activity in annulus fibrosus cells by upregulating lipocalin 2 expression. Eur Spine J, 2015, 24(9): 1959-1968.
36.	Kao TH, Peng YJ, Tsou HK, et al. Nerve growth factor promotes expression of novel genes in intervertebral disc cells that regulate tissue degradation: Laboratory investigation. J Neurosurg Spine, 2014, 21(4): 653-661.
37.	Paesold G, Nerlich AG, Boos N. Biological treatment strategies for disc degeneration: potentials and shortcomings. Eur Spine J, 2007, 16(4): 447-468.
38.	Cha YJ, Koo JS. Adipokines as therapeutic targets in breast cancer treatment. Expert Opin Ther Targets, 2018, 22(11): 941-953.
39.	Chung HS, Choi KM. Adipokines and myokines: a pivotal role in metabolic and cardiovascular disorders. Curr Med Chem, 2018, 25(20): 2401-2415.
40.	Pramanik S, Rathwa N, Patel R, et al. Treatment avenues for type 2 diabetes and current perspectives on adipokines. Curr Diabetes Rev, 2018, 14(3): 201-221.
41.	Francisco V, Ruiz-Fernández C, Pino J, et al. Adipokines: Linking metabolic syndrome, the immune system, and arthritic diseases. Biochem Pharmacol, 2019, 165: 196-206.

1. Sampara P, Banala RR, Vemuri SK, et al. Understanding the molecular biology of intervertebral disc degeneration and potential gene therapy strategies for regeneration: a review. Gene Ther, 2018, 25(2): 67-82.
2. Kadow T, Sowa G, Vo N, et al. Molecular basis of intervertebral disc degeneration and herniations: what are the important translational questions? Clin Orthop Relat Res, 2015, 473(6): 1903-1912.
3. 侯孝忠, 徐林飞, 易威威, 等. 内质网应激对吸烟诱导的髓核细胞凋亡与炎性反应的影响研究. 中国修复重建外科杂志, 2019, 33(6): 736-742.
4. 陈琪, 石芳芳, 杨曦, 等. 不同代次髓核细胞生物学特性的比较研究. 中国修复重建外科杂志, 2018, 32(6): 660-667.
5. MacDonald IJ, Liu SC, Huang CC, et al. Associations between adipokines in arthritic disease and implications for obesity. Int J Mol Sci, 2019, 20(6): pii: E1505.
6. Ruiz-Fernández C, Francisco V, Pino J, et al. Molecular relationships among obesity, inflammation and intervertebral disc degeneration: are adipokines the common link? Int J Mol Sci, 2019, 20(8): pii: E2030.
7. Fasshauer M, Blüher M. Adipokines in health and disease. Trends Pharmacol Sci, 2015, 36(7): 461-470.
8. Gandhi R, Sharma A, Kapoor M, et al. Racial differences in serum adipokine and insulin levels in a matched osteoarthritis sample: a pilot study. J Obes, 2016, 2016: 8746268.
9. Ouchi N, Parker JL, Lugus JJ, et al. Adipokines in inflammation and metabolic disease. Nat Rev Immunol, 2011, 11(2): 85-97.
10. Dowdell J, Erwin M, Choma T, et al. Intervertebral disk degeneration and repair. Neurosurgery, 2017, 80(3S): S46-S54.
11. Segar AH, Fairbank JCT, Urban J. Leptin and the intervertebral disc: a biochemical link exists between obesity, intervertebral disc degeneration and low back pain-an in vitro study in a bovine model. Eur Spine J, 2019, 28(2): 214-223.
12. Francisco V, Pino J, Campos-Cabaleiro V, et al. Obesity, fat mass and immune system: role for leptin. Front Physiol, 2018, 9: 640.
13. Zhao CQ, Liu D, Li H, et al. Expression of leptin and its functional receptor on disc cells: contribution to cell proliferation. Spine (Phila Pa 1976), 2008, 33(23): E858-E864.
14. Li Z, Shen J, Wu WK, et al. Leptin induces cyclin D1 expression and proliferation of human nucleus pulposus cells via JAK/STAT, PI3K/Akt and MEK/ERK pathways. PLoS One, 2012, 7(12): e53176.
15. Li Z, Yu X, Liang J, et al. Leptin downregulates aggrecan through the p38-ADAMST pathway in human nucleus pulposus cells. PLoS One, 2014, 9(10): e109595.
16. Han YC, Ma B, Guo S, et al. Leptin regulates disc cartilage endplate degeneration and ossification through activation of the MAPK-ERK signalling pathway in vivo and in vitro. J Cell Mol Med, 2018, 22(4): 2098-2109.
17. Liu M, Liu F. Regulation of adiponectin multimerization, signaling and function. Best Pract Res Clin Endocrinol Metab, 2014, 28(1): 25-31.
18. Yamauchi T, Iwabu M, Okada-Iwabu M, et al. Adiponectin receptors: a review of their structure, function and how they work. Best Pract Res Clin Endocrinol Metab, 2014, 28(1): 15-23.
19. Yuan B, Huang L, Yan M, et al. Adiponectin downregulates TNF-α expression in degenerated intervertebral discs. Spine (Phila Pa 1976), 2018, 43(7): E381-E389.
20. Terashima Y, Kakutani K, Yurube T, et al. Expression of adiponectin receptors in human and rat intervertebral disc cells and changes in receptor expression during disc degeneration using a rat tail temporary static compression model. J Orthop Surg Res, 2016, 11(1): 147.
21. Jamaluddin MS, Weakley SM, Yao Q, et al. Resistin: functional roles and therapeutic considerations for cardiovascular disease. Br J Pharmacol, 2012, 165(3): 622-632.
22. Fang WQ, Zhang Q, Peng YB, et al. Resistin level is positively correlated with thrombotic complications in Southern Chinese metabolic syndrome patients. J Endocrinol Invest, 2011, 34(2): e36-e42.
23. Li Z, Wang X, Pan H, et al. Resistin promotes CCL4 expression through toll-like receptor-4 and activation of the p38-MAPK and NF-κB signaling pathways: implications for intervertebral disc degeneration. Osteoarthritis Cartilage, 2017, 25(2): 341-350.
24. Liu C, Yang H, Gao F, et al. Resistin Promotes Intervertebral Disc Degeneration by Upregulation of ADAMTS-5 Through p38 MAPK Signaling Pathway. Spine (Phila Pa 1976), 2016, 41(18): 1414-1420.
25. Wei J, Hettinghouse A, Liu C. The role of progranulin in arthritis. Ann N Y Acad Sci, 2016, 1383(1): 5-20.
26. Zhao YP, Tian QY, Liu B, et al. Progranulin knockout accelerates intervertebral disc degeneration in aging mice. Sci Rep, 2015, 5: 9102.
27. Wang S, Wei J, Fan Y, et al. Progranulin is positively associated with intervertebral disc degeneration by interaction with IL-10 and IL-17 through TNF pathways. Inflammation, 2018, 41(5): 1852-1863.
28. Francisco V, Pérez T, Pino J, et al. Biomechanics, obesity, and osteoarthritis. The role of adipokines: When the levee breaks. J Orthop Res, 2018, 36(2): 594-604.
29. Radzicka S, Pietryga M, Iciek R, et al. The role of visfatin in pathogenesis of gestational diabetes (GDM). Ginekol Pol, 2018, 89(9): 518-521.
30. Shi C, Wu H, Du D, et al. Nicotinamide phosphoribosyltransferase inhibitor APO866 prevents IL-1β-induced human nucleus pulposus cell degeneration via autophagy. Cell Physiol Biochem, 2018, 49(6): 2463-2482.
31. Colldén G, Tschöp MH, Müller TD. Therapeutic potential of targeting the ghrelin pathway. Int J Mol Sci, 2017, 18(4): pii: E798.
32. Pereira JADS, da Silva FC, de Moraes-Vieira PMM. The impact of ghrelin in metabolic diseases: an immune perspective. J Diabetes Res, 2017, 2017: 4527980.
33. Li W, Wu X, Qu R, et al. Ghrelin protects against nucleus pulposus degeneration through inhibition of NF-κB signaling pathway and activation of Akt signaling pathway. Oncotarget, 2017, 8(54): 91887-91901.
34. Francisco V, Pino J, Gonzalez-Gay MA, et al. Adipokines and inflammation: is it a question of weight? Br J Pharmacol, 2018, 175(10): 1569-1579.
35. Kao TH, Peng YJ, Salter DM, et al. Nerve growth factor increases MMP9 activity in annulus fibrosus cells by upregulating lipocalin 2 expression. Eur Spine J, 2015, 24(9): 1959-1968.
36. Kao TH, Peng YJ, Tsou HK, et al. Nerve growth factor promotes expression of novel genes in intervertebral disc cells that regulate tissue degradation: Laboratory investigation. J Neurosurg Spine, 2014, 21(4): 653-661.
37. Paesold G, Nerlich AG, Boos N. Biological treatment strategies for disc degeneration: potentials and shortcomings. Eur Spine J, 2007, 16(4): 447-468.
38. Cha YJ, Koo JS. Adipokines as therapeutic targets in breast cancer treatment. Expert Opin Ther Targets, 2018, 22(11): 941-953.
39. Chung HS, Choi KM. Adipokines and myokines: a pivotal role in metabolic and cardiovascular disorders. Curr Med Chem, 2018, 25(20): 2401-2415.
40. Pramanik S, Rathwa N, Patel R, et al. Treatment avenues for type 2 diabetes and current perspectives on adipokines. Curr Diabetes Rev, 2018, 14(3): 201-221.
41. Francisco V, Ruiz-Fernández C, Pino J, et al. Adipokines: Linking metabolic syndrome, the immune system, and arthritic diseases. Biochem Pharmacol, 2019, 165: 196-206.

Previous Article
Wound-induced hair follicle neogenesis: a new perspective on hair follicles regeneration in adult mammals
Next Article
Progress of hip fracture treatment in children

Chinese Journal of Reparative and Reconstructive Surgery

Research progress on the role of adipokines in intervertebral disc degeneration

Abstract Full text Figures/Tables Video References Cited by

Previous Article

Next Article

Format

Content