Obesity-Induced Osteoarthritis: the Multifactorial Association and Leading Role of Adipokines, Dyslipidemia and Mechanical Loading

I.Yu. Golovach


The article discribes current data and recent studies on possible connection between obesity, osteoarthritis and аdipokines. Obesity is a well-known risk factor for development of osteoarthritis. The link between overweight and osteoarthritis cannot be explained by the increased joint load accompanying obesity. However, the association between obesity and osteoarthritis in non-weight-bearing joints suggests a more complex aetiology for obesity-induced weight-bearing. Today, adipose tissue is regarded as an endocrine organ that produces substances with local and systemic effects. The best-known and well researched аdipokines are leptin, adiponectin, resistin and visfatin, the role of which in the pathogenesis of osteoarthritis and other rheumatic diseases is discussed extensively. Adipokines may influence articular cartilage in different ways. On the one hand, they raise the level of proinflammatory factors; on the other hand they have anti-inflammatory potential. Subsequently, the effects of a lipid dysmetabolism, low-grade inflammation on joint tissues are discussed and linked to osteoarthritis. Thus, the association between obesity and osteoarthritis is beyond the mechanical loading and generates separate clinical-pathogenic phenotype of the disease.


osteoarthritis; obesity; adipokines; dyslipidemia; pathogenesis


Alekseeva L.I., Zaiceva E.M. Rol subhondral’noi kosti pri osteoartroze. Nauchno-praktich. revmatologiya. 2009; 4: 41-48.

Babak O.Ya., Klimenko N.N. Fiziologicheskaya i patofiziologicheskaya rol adiponektina v kompleksnom regulirovanii obmena veshestv i razvitii serdechno-sosudistyh zabolevanii. Ukr. terapevt. zhurnal. 2010; 2: 94-100.

Golovach I.Yu. Osteoartrit: fundamental’nye i prikladnye aspekty etiopatogeneza zabolevaniya. Nichego ne stoit na meste. Ukr. revmatol. zhurnal. 2014; 1(56): 4-11.

Golovach I.Yu. Osteoartroz i adipokiny: patogenetichni zv’yazki, vpliv na suglobovii hryash ta novitni terapevtichni cili. Mistectvo likuvannya. 2011; 8(84): 34-38.

Denisov L.N., Nasonov E.L. Ozhirenie i osteoartroz. Nauchno-praktich. revmatologiya. 2010; ¹3: 48-51.

Kovaleva O.N., Ambrosova T.N., Asheulova T.V., Getman E.A. Adipokiny: biologicheskie, patofiziologicheskie i metabolicheskie effekty. Vnutrennyaya medicina. 2009; 3(15): 32-38.

Castaceda S., Roman-Blas J.A., Largo R., Herrero-Beaumont G. Osteoarthritis: a progressive disease with changing phenotypes. Rheumatology. 2013; 6: 258-260. doi: 10.1093/rheumatology/ket247.

Chen X.X., Yang T. Roles of leptin in bone metabolism and bone diseases. J Bone Miner Metab. 2015; 68 (3): 33-37.

Clockaerts S., Bastiaansen-Jenniskens Y.M. Feijt C. et al. Cytokine production by infrapatellar fat pad can be stimulated by interleukin 1beta and inhibited by peroxisome proliferator activated receptor alpha agonist. Ann Rheum Dis 2012; 71: 1012–1028. doi: 10.1136/annrheumdis-2011-200688.

Conaghan P.G., Vanharanta H., Dieppe P.A. Is progressive osteoarthritis an atheromatous vascular disease? Ann. Rheum. Dis. 2005; 64: 1539-1541. doi:10.1136/ard.2005.039263.

Dahaghin S., Bierma-Zeinstra S.M., Koes B.W., Hazes J.M., Pols H.A. Do metabolic factors add to the effect of overweight on hand osteoarthritis? The Rotterdam Study. Ann Rheum Dis 2007; 66: 916–920. doi: 10.1136/ard.2005.045724

Gegout P.P., Francin P.J., Mainard D., Presle N. Adipokines in osteoarthritis: friends or foes of cartilage homeostasis? Joint. Bone. Spine. 2008; 75(6): 669-671. doi: 10.1016/j.jbspin.2008.07.008.

Grotle M., Hagen K.B., Natvig B., Dahl F.A., Kvien T.K. Obesity and osteoarthritis in knee, hip and/or hand: an epidemiological study in the general population with 10 years follow-up. BMC Musculoskelet Disord. 2008; 9: 132. doi:10.1186/1471-2474-9-132.

Gualillo O. Further evidence for leptin involvement in cartilage homeostases. Osteoarthritis Cartilage. 2007; 15(8): 857-860. doi: http://dx.doi.org/10.1016/j.joca.2007.04.015

Guilak F. Biomechanical factors in osteoarthritis. Best Pract. Res. Clin. Rheumatol., 2011; 25(6): 815-823. doi: 10.1016/j.berh.2011.11.013.

Harding G.T., Hubley-Kozey C.L., Dunbar M.J., Stanish W.D., Astephen Wilson J.L. Body mass index affects knee joint mechanics during gait differently with and without moderate knee osteoarthritis. Osteoarthritis and Cartilage. 2012; 20: 1234–1242. doi: 10.1016/j.joca.2012.08.004.

Hoff P., Buttgereit F., Burmester G.R. et al. Osteoarthritis synovial fluid activates pro-inflammatory cytokines in primary human chondrocytes. Int. Orthop. 2013; 37: 145–151. doi: 10.1007/s00264-012-1724-1.

Iwata M., Ochi H., Hara Y. et al. Initial responses of articular tissues in a murine high-fat diet-induced osteoarthritis model: pivotal role of the IPFP as a cytokine fountain. PloS One. 2013; 8: e60706. doi: 10.1371/journal.pone.0060706.

Kanata S., Akagi M., Nishimura S. et al. Oxidized LDL binding to LOX-1 upregulates VEGF expression in cultured bovine chondrocytes through activation of PPAR-gamma. Biochem. Biophys. Res. Commun. 2006; 348: 1003-1010. doi:10.1016/j.bbrc.2006.07.133.

Klop B., Elte J.W., Cabezas M.C. Dyslipidemia in obesity: mechanisms and potential targets. Nutrients. 2013; 5: 1218–1240. doi: 10.3390/nu5041218.

Ko F.C., Dragomir C., Plumb D.A. et al. In vivo cyclic compression causes cartilage degeneration and subchondral bone changes in mouse tibiae. Arthritis Rheum. 2013; 65: 1569–1578. DOI: 10.1002/art.37906

Krenning G., Moonen J.R., Harmsen M.C. Pleiotropism of adiponectin: inflammation, neovascularization, and fibrosis. Circ Res. 2009; 104: 1029-1031. doi: 10.1161/CIRCRESAHA.109.198044.

Lajeunesse D., Massicotte F., Pelletier J.P., Martel-Pelletier J. Subchondral bone sclerosis in osteoarthritis: not Just an innocent bystander. Mod. Rheumatol. 2003;13: 7–14. doi: 10.3109/s101650300001.

Laurberg T.B., Frystyk J., Ellingsen T. et al. Plasma adiponectin in patients with active, early, and chronic rheumatoid arthritis who are steroid- and disease-modifying antirheumatic drug-naive compared with patients with osteoarthritis and controls. J. Rheumatol. 2009; 36: 1885–1891. doi: 10.3899/jrheum.080907.

Lee J.H., Ort T., Ma K., et al. Resistin is elevated following traumatic joint injury and causes matrix degradation and release of inflammatory cytokines from articular cartilage in vitro. Osteoarthritis Cartilage. 2009; 17(5): 613-620. doi: 10.1016/j.joca.2008.08.007.

Loeser R.F., Goldrina S.R., Scanzello C.R. et al. Osteoarthritis: A Disease of the Joint as an Organ. Arthritis Rheum. 2012; 64(6): 1697-1707. doi: 10.1002/art.34453.

Murata M., Yudoh K., Masuko K. The potential role of vascular endothelial growth factor (VEGF) in cartilage: how the angiogenic factor could be involved in the pathogenesis of osteoarthritis? Osteoarthritis Cartilage. 2008;16: 279–286. doi:10.1016/j.joca.2007.09.003

Nguyen M.T., Favelyukis S., Nguyen A.K. et al. A subpopulation of macrophages infiltrates hypertrophic adipose tissue and is activated by free fatty acids via Toll-like receptors 2 and 4 and JNK-dependent pathways. J. Biol. Chem. 2007; 282: 35279–35292. doi:10.1074/jbc.M706762200

Otero M., Lago R., Gomez R., et al. Changes in plasma levels of fat-derived hormones adiponectin, leptin, resistin and visfatin in patients with rheumatoid arthritis. Ann. Rheum. Dis. 2006; 65: 1198-1201. doi: 10.1136/ard.2005.046540

Pufe T., Harde V., Petersen W. et al. Vascular endothelial growth factor (VEGF) induces matrix metalloproteinase expression in immortalized chondrocytes. J. Pathol. 2004; 202: 367-374. DOI: 10.1002/path.1527

Radin E.L., Paul I.L., Rose R.M. Role of mechanical factors in pathogenesis of primary osteoarthritis. Lancet 1972; 1: 519–22.

Rosen E.D., Spiegelman B.M. Adipocytes as regulators of energy balance and glucose homeostasis. Nature. 2006; 444: 847-853. doi: 10.1038/nature05483

Rowan A.D., Koshy P.J., Shingleton W.D. et al. Synergistic effects of glycoprotein 130 binding cytokines in combination with interleukin-1 on cartilage collagen breakdown. Arthritis Rheum. 2001; 44: 1620-1632. DOI: 10.1002/1529-0131(200107)44:7<1620::AID-ART285>3.0.CO;2-B

Sellam J., Berenbaum F. Is osteoarthritis a metabolic disease? Joint Bone Spine. 2013; 80(6): 568-573. doi: 10.1016/j.jbspin.2013.09.007.

Simopoulou T., Malizos K.N., Iliopoulos D. et al. Differential expression of leptin and leptin’s receptor isoform (Ob-Rb) mRNA between advanced and minimally affected osteoarthritic cartilage: effect on cartilage metabolism. Osteoarthritis Cartilage. 2007; 15: 872-883. doi:10.1016/j.joca.2007.01.018

Simopoulou T., Malizos K.N., Tsezou A. Lectin-like oxidized low density lipoprotein receptor 1 (LOX-1) expression in human articular chondrocytes. Clin. Exp. Rheumatol. 2007; 25: 605–612.

Soran N., Altindag O., Cakir H. et al. Assessment of paraoxonase activities in patients with knee osteoarthritis. Redox Rep. 2008; 13: 194–198. doi: 10.1179/135100008X308911.

Stannus O., Jones G., Cicuttini F. et al. Circulating levels of IL-6 and TNF-alpha are associated with knee radiographic osteoarthritis and knee cartilage loss in older adults. Osteoarthritis Cartilage. 2010; 18: 1441–1447. doi: 10.1016/j.joca.2010.08.016.

Stevens A.L., Wishnok J.S., White F.M., Grodzinsky A.J., Tannenbaum S.R. Mechanical injury and cytokines cause loss of cartilage integrity and upregulate proteins associated with catabolism, immunity, inflammation, and repair. Mol. Cell Proteomics. 2009; 8(7): 1475-1489. doi: 10.1074/mcp.M800181-MCP200.

Sturmer T., Gunther K.P., Brenner H. Obesity, overweight and patterns of osteoarthritis: the Ulm Osteoarthritis Study. J Clin Epidemiol 2000; 53: 307–313. DOI: http://dx.doi.org/10.1016/S0895-4356(99)00162-6

Thijssen E., van Caam A., van der Kraan P.M. Obesity and Osteoarthritis, More Than Just Wear and Tear: Pivotal Roles for Inflamed Adipose Tissue and Dyslipidaemia in Obesity-induced Osteoarthritis. Rheumatology. 2015; 54(4): 588-600. doi: 10.1093/rheumatology/keu464.

Ushiyama T., Chano T., Inoue K., Matsusue Y. Cytokine production in the infrapatellar fat pad: another source of cytokines in knee synovial fluids. Ann. Rheum. Dis. 2003; 62: 108–112.

Wang X., Hunter D., Xu J., Ding C. Metabolic triggered inflammation in osteoarthritis. Osteoarthritis Cartilage. 2015; 23(1): 22-30. doi: 10.1016/j.joca.2014.10.002.

Weisberg SP, McCann D, Desai M et al. Obesity is associated with macrophage accumulation in adipose tissue. J. Clin. Invest. 2003;112: 1796–1808. doi:10.1172/JCI19246.

Wluka А.Е., Lombard C.B., Cicuttini F.M. Tackling obesity in knee osteoarthritis. Nat. Rev. Rheumat. 2013; 9: 225-235. doi: 10.1038/nrrheum.2012.224.

DOI: https://doi.org/10.22141/1608-1706.4.16.2015.80172


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