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Osteoarthritis: More than Cartilage Degeneration

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Abstract

Osteoarthritis (OA) is nowadays considered as a global disease of the joint in which all articular structures are involved. Although articular cartilage is the primary target of the disease, both subchondral bone (SB) and synovium are structures that actively participate at the onset and in the progression of the disease. The relationship between these three structures is variable and mutable according to their evolution and the initial triggers. Pathogenic mechanisms will also vary depending on the predominant phenotype of OA in each patient. In this review, we emphasize the role of synovial membrane and SB in the onset and progression of the disease. Moreover, we review the current concepts of the cross talk between SB and articular cartilage and their biomechanical and functional properties. The participation of different structures in the OA pathogenesis will allow new therapeutic approaches directed to the main joint structures involved in every moment of the disease.

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References

  1. Arden N, Nevitt MC. Osteoarthritis: epidemiology. Best Pract Res Clin Rheumatol. 2006;20:3–25.

    Article  PubMed  Google Scholar 

  2. Blagojevic M, Jinks C, Jeffery A, Jordan KP. Risk factors for onset of osteoarthritis of the knee in older adults: a systematic review and meta-analysis. Osteoarthr Cartil. 2010;18:24–33.

    Article  CAS  PubMed  Google Scholar 

  3. Toivanen AT, Heliövaara M, Impivaara O, Arokoski JP, Knekt P, Lauren H, et al. Obesity, physically demanding work and traumatic knee injury are major risk factors for knee osteoarthritis—a population-based study with a follow-up of 22 years. Rheumatology (Oxford). 2010;49:308–14.

    Article  Google Scholar 

  4. Wieland HA, Michaelis M, Kirschbaum BJ, Rudolphi KA. Osteoarthritis-an untreatable disease? Nat Rev Drug Discov. 2005;4:331–44.

    Article  CAS  PubMed  Google Scholar 

  5. Loeser RF, Goldring SR, Scanzello CR, Goldring MB. Osteoarthritis: a disease of the joint as an organ. Arthritis Rheum. 2012;64:1697–707.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Goldring MB, Goldring SR. Articular cartilage and subchondral bone in the pathogenesis of osteoarthritis. Ann N Y Acad Sci. 2010;1192:230–7.

    Article  CAS  PubMed  Google Scholar 

  7. Burr DB, Gallant MA. Bone remodelling in osteoarthritis. Nat Rev Rheumatol. 2012;8:665–73.

    Article  CAS  PubMed  Google Scholar 

  8. Henrotin Y, Pesesse L, Sanchez C. Subchondral bone and osteoarthritis: biological and cellular aspects. Osteoporos Int. 2012;23:S847–51.

    Article  PubMed  Google Scholar 

  9. Felson DT. Clinical practice. Osteoarthritis of the knee. N Engl J Med. 2006;354:841–8.

    Article  CAS  PubMed  Google Scholar 

  10. Herrero-Beaumont G, Roman-Blas JA, Castañeda S, Jimenez SA. Primary osteoarthritis no longer primary: three subsets with distinct etiological, clinical, and therapeutic characteristics. Semin Arthritis Rheum. 2009;39:71–80.

    Article  PubMed  Google Scholar 

  11. Heinegard D, Saxne T. The role of the cartilage matrix in osteoarthritis. Nat Rev Rheumatol. 2011;7:50–6.

    Article  PubMed  CAS  Google Scholar 

  12. Onnerfjord P, Khabut A, Reinholt FP, Svensson O, Heinegard D. Quantitative proteomic analysis of eight cartilaginous tissues reveals characteristic differences as well as similarities between subgroups. J Biol Chem. 2012;287:18913–24.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Hunziker EB, Lippuner K, Shintani N. How best to preserve and reveal the structural intricacies of cartilaginous tissue. Matrix Biol. 2014;39:33–43.

    Article  CAS  PubMed  Google Scholar 

  14. Goldring SR, Goldring MB. Changes in the osteochondral unit during osteoarthritis: structure, function and cartilage-bone crosstalk. Nat Rev Rheumatol. 2016;12:632–44.

    Article  PubMed  Google Scholar 

  15. Andriacchi TP, Favre J. The nature of in vivo mechanical signals that influence cartilage health and progression to knee osteoarthritis. Curr Rheumatol Rep. 2014;16:463.

    Article  PubMed  Google Scholar 

  16. Guo H, Maher SA, Torzilli PA. A biphasic finite element study on the role of the articular cartilage superficial zone in confined compression. J Biomech. 2015;48:166–70.

    Article  PubMed  Google Scholar 

  17. Greene GW, et al. Adaptive mechanically controlled lubrication mechanism found in articular joints. Proc Natl Acad Sci U S A. 2011;108:5255–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Hunziker EB, Kapfinger E, Geiss J. The structural architecture of adult mammalian articular cartilage evolves by a synchronized process of tissue resorption and neoformation during postnatal development. Osteoarthr Cartil. 2007;15:403–13.

    Article  CAS  PubMed  Google Scholar 

  19. Pfander D, Gelse K. Hypoxia and osteoarthritis: how chondrocytes survive hypoxic environments. Curr Opin Rheumatol. 2007;19:457–62.

    Article  CAS  PubMed  Google Scholar 

  20. Thoms BL, Dudek KA, Lafont JE, Murphy CL. Hypoxia promotes the production and inhibits the destruction of human articular cartilage. Arthritis Rheum. 2013;65:1302–12.

    Article  CAS  PubMed  Google Scholar 

  21. Maes C, Araldi E, Haigh K, Khatri R, Van Looveren R, Giaccia AJ, et al. VEGF-independent cell-autonomous functions of HIF-1α regulating oxygen consumption in fetal cartilage are critical for chondrocyte survival. J Bone Miner Res. 2012;27:596–609.

    Article  CAS  PubMed  Google Scholar 

  22. Burr D. Anatomy and physiology of the mineralized tissues: role in the pathogenesis of osteoarthrosis. Osteoarthritis Cartilage. 2004;(Suppl. A):S20–30.

  23. Suri S, Walsh DA. Osteochondral alterations in osteoarthritis. Bone. 2012;51:204–11.

    Article  PubMed  Google Scholar 

  24. Imhof H, Sulzbacher I, Grampp S, Czerny C, Youssefzadeh S, Kainberger F. Subchondral bone and cartilage disease: a rediscovered functional unit. Investig Radiol. 2000;35:581–8.

    Article  CAS  Google Scholar 

  25. Goldring SR. Alterations in periarticular bone and cross talk between subchondral bone and articular cartilage in osteoarthritis. Ther Adv Musculoskelet Dis. 2012;4:249–58.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Lories RJ, Luyten FP. The bone-cartilage unit in osteoarthritis. Nat Rev Rheumatol. 2011;7:43–9.

    Article  CAS  PubMed  Google Scholar 

  27. Mahjoub M, Berenbaum F, Houard X. Why subchondral bone in osteoarthritis? The importance of the cartilage bone interface in osteoarthritis. Osteoporos Int. 2012;23(Suppl 8):S841–6.

    Article  PubMed  Google Scholar 

  28. Milz S, Putz R. Quantitative morphology of the subchondral plate of the tibial plateau. J Anat. 1994;185:103–10.

    PubMed  PubMed Central  Google Scholar 

  29. Castañeda S, Roman-Blas JA, Largo R, Herrero-Beaumont G. Subchondral bone as a key target for osteoarthritis treatment. Biochem Pharmacol. 2012;83:315–23.

    Article  PubMed  CAS  Google Scholar 

  30. Roberts S, Weightman B, Urban J, Chappell D. Mechanical and biochemical properties of human articular cartilage in osteoarthritic femoral heads and in autopsy specimens. J Bone Joint Surg Br. 1986;68:278–88.

    CAS  PubMed  Google Scholar 

  31. Calvo E, Palacios I, Delgado E, Sánchez-Pernaute O, Largo R, Egido J, et al. Histopathological correlation of cartilage swelling detected by magnetic resonance imaging in early experimental osteoarthritis. Osteoarthr Cartil. 2004;12:878–86.

    Article  CAS  PubMed  Google Scholar 

  32. Wang M, Sampson ER, Jin H, Li J, Ke QH, Im HJ, et al. MMP13 is a critical target gene during the progression of osteoarthritis. Arthritis Res Ther. 2013;15:R5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Walsh DA, McWilliams DF, Turley MJ, Dixon MR, Fransès RE, Mapp PI, et al. Angiogenesis and nerve growth factor at the osteochondral junction in rheumatoid arthritis and osteoarthritis. Rheumatology (Oxford). 2010;49:1852–61.

    Article  CAS  Google Scholar 

  34. Bullough PG, et al. Osteoarthr Cartil. 2004;12(Suppl. A):S2–9.

    Article  PubMed  Google Scholar 

  35. Hashimoto S, Creighton-Achermann L, Takahashi K, Amiel D, Coutts RD, et al. Development and regulation of osteophyte formation during experimental osteoarthritis. Osteoarthr Cartil. 2002;10:180–7.

    Article  CAS  PubMed  Google Scholar 

  36. Houard X, Goldring MB, Berenbaum F. Homeostatic mechanisms in articular cartilage and role of inflammation in osteoarthritis. Curr Rheumatol Rep. 2013;15:375.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  37. Liu-Bryan R, Terkeltaub R. Emerging regulators of the inflammatory process in osteoarthritis. Nat Rev Rheumatol. 2015;11:35–44.

    Article  CAS  PubMed  Google Scholar 

  38. Li G, Yin J, Gao J, Cheng TS, Pavlos NJ, Zhang C, et al. Subchondral bone in osteoarthritis: insight into risk factors and microstructural changes. Arthritis Res Ther. 2013;15:223.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Anderson-MacKenzie JM, Quasnichka HL, Starr RL, Lewis EJ, Billingham ME, Bailey AJ. Fundamental subchondral bone changes in spontaneous knee osteoarthritis. Int J Biochem Cell Biol. 2005;37:224–36.

    Article  CAS  PubMed  Google Scholar 

  40. Carlson CS, Loeser RF, Purser CB, Gardin JF, Jerome CP. Osteoarthritis in cynomolgus macaques. III. Effects of age, gender, and subchondral bone thickness on the severity of disease. J Bone Miner Res. 1996;11:1209–17.

    Article  CAS  PubMed  Google Scholar 

  41. Rogers J, Shepstone L, Dieppe P. Is osteoarthritis a systemic disorder of bone? Arthritis Rheum. 2004;50:452–7.

    Article  PubMed  Google Scholar 

  42. Calvo E, Castañeda S, Largo R, Fernández-Valle ME, Rodríguez-Salvanés F, Herrero-Beaumont G. Osteoporosis increases the severity of cartilage damage in an experimental model of osteoarthritis in rabbits. Osteoarthr Cartil. 2007;15:69–77.

    Article  CAS  PubMed  Google Scholar 

  43. Bellido M, Lugo L, Roman-Blas JA, Castañeda S, Caeiro JR, Dapia S, et al. Subchondral bone microstructural damage by increased remodelling aggravates experimental osteoarthritis preceded by osteoporosis. Arthritis Res Ther. 2010;12:R152.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  44. Pan J, Zhou X, Li W, Novotny JE, Doty SB, Wang L. In situ measurement of transport between subchondral bone and articular cartilage. J Orthop Res. 2009;27:1347–52.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Intema F, Sniekers YH, Weinans H, Vianen ME, Yocum SA, Zuurmond AM, et al. Similarities and discrepancies in subchondral bone structure in two differently induced canine models of osteoarthritis. J Bone Miner Res. 2010;25:1650–7.

    Article  PubMed  Google Scholar 

  46. Sniekers YH, Intema F, Lafeber FP, van Osch GJ, van Leeuwen JP, Weinans H, et al. A role for subchondral bone changes in the process of osteoarthritis; a micro-CT study of two canine models. BME Musculoskelet Disord. 2008;9:20.

    Article  Google Scholar 

  47. Reichenbach S, Guermazi A, Niu J, Neogi T, Hunter DJ, Roemer FW, et al. Prevalence of bone attrition on knee radiographs and MRI in a community-based cohort. Osteoarthr Cartil. 2008;16:1005–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Bettica P, Cline G, Hart DJ, Meyer J, Spector TD. Evidence for increased bone resorption in patients with progressive knee osteoarthritis: longitudinal results from the Chingford study. Arthritis Rheum. 2002;46:3178–84.

    Article  PubMed  Google Scholar 

  49. Bolbos RI, Zuo J, Banerjee S, Link TM, Ma CB, Li X, et al. Relationship between trabecular bone structure and articular cartilage morphology and relaxation times in early OA of the knee joint using parallel MRI at 3T. Osteoarthr Cartil. 2008;16:1150–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Li ZC, Dai LY, Jiang LS, Qiu S. Difference in subchondral cancellous bone between postmenopausal women with hip osteoarthritis and osteoporotic fracture: implication for fatigue microdamage, bone microarchitecture, and biomechanical properties. Arthritis Rheum. 2012;64:3955–62.

    Article  PubMed  Google Scholar 

  51. Malekipour F, Whitton C, Oetomo D, Lee PV. Shock absorbing ability of articular cartilage and subchondral bone under impact compression. J Mech Behav Biomed Mater. 2013;26:127–35.

    Article  PubMed  Google Scholar 

  52. Fazzalari NL, Kuliwaba JS, Forwood MR. Cancellous bone microdamage in the proximal femur: influence of age and osteoarthritis on damage morphology and regional distribution. Bone. 2002;31:697–702.

    Article  CAS  PubMed  Google Scholar 

  53. Bentolila V, Boyce TM, Fyhrie DP, Drumb R, Skerry TM, Schaffler MB. Intracortical remodeling in adult rat long bones after fatigue loading. Bone. 1998;23:275–81.

    Article  CAS  PubMed  Google Scholar 

  54. Verborgt O, Gibson GJ, Schaffler MB. Loss of osteocyte integrity in association with microdamage and bone remodeling after fatigue in vivo. J Bone Miner Res. 2000;15:60–7.

    Article  CAS  PubMed  Google Scholar 

  55. Nakashima T, Hayashi M, Fukunaga T, Kurata K, Oh-Hora M, Feng JQ, et al. Evidence for osteocyte regulation of bone homeostasis through RANKL expression. Nat Med. 2011;17:1231–4.

    Article  CAS  PubMed  Google Scholar 

  56. Kennedy OD, Herman BC, Laudier DM, Majeska RJ, Sun HB, Schaffler MB. Activation of resorption in fatigue-loaded bone involves both apoptosis and active pro-osteoclastogenic signaling by distinct osteocyte cell populations. Bone. 2012;50:1115–22.

    Article  PubMed  PubMed Central  Google Scholar 

  57. Goldring MB, Goldring SR. Osteoarthritis. J Cell Physiol. 2007;213:626–34.

    Article  CAS  PubMed  Google Scholar 

  58. Massicotte F, Lajeunesse D, Benderdour M, Pelletier JP, Hilal G, Duval N, et al. Can altered production of interleukin-1beta, interleukin-6, transforming growth factor-beta and prostaglandin E(2) by isolated human subchondral osteoblasts identify two subgroups of osteoarthritic patients. Osteoarthr Cartil. 2002;10:491–500.

    Article  CAS  PubMed  Google Scholar 

  59. Brown RA, Weiss JB. Neovascularisation and its role in the osteoarthritic process. Ann Rheum Dis. 1988;47:881–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Luyten FR, Lories RJU, Verschueren P, de Vlam K, Westhovens R. Contemporary concepts of inflammation, damage and repair in rheumatic diseases. Best Pract Res Clin Rheumatol. 2006;5:829–48.

    Article  CAS  Google Scholar 

  61. Kim HR, So Y, Moon SG, Lee IS, Lee SH. Clinical value of 9mTc-methylene diphosphonate (MDP) bone single photon emission computed tomography (SPECT) in patients with knee osteoarthritis. Osteoarthr Cartil. 2008;16:212–8.

    Article  PubMed  Google Scholar 

  62. Addison S, Coleman RE, Feng S, McDaniel G, Kraus VB. Whole-body bone scintigraphy provides a measure of the total-body burden of osteoarthritis for the purpose of systemic biomarker validation. Arthritis Rheum. 2009;60:3366–73.

    Article  PubMed  PubMed Central  Google Scholar 

  63. Day JS, et al. Adaptation of subchondral bone in osteoarthritis. Biorheology. 2004;41:359–68.

    CAS  PubMed  Google Scholar 

  64. Buckland-Wright C. Subchondral bone changes in hand and knee osteoarthritis detected by radiography. Osteoarthr Cartil. 2004;12(Suppl. A):S10–9.

    Article  PubMed  Google Scholar 

  65. Li B, Aspden RM. Composition and mechanical properties of cancellous bone from the femoral head of patients with osteoporosis and osteoarthritis. J Bone Miner Res. 1997;12:641–51.

    Article  CAS  PubMed  Google Scholar 

  66. Taljanovic MS, Graham AR, Benjamin JB, Gmitro AF, Krupinski EA, Schwartz SA, et al. Bone marrow edema pattern in advanced hip osteoarthritis: quantitative assessment with magnetic resonance imaging and correlation with clinical examination, radiographic findings, and histopathology. Skelet Radiol. 2008;37:423–31.

    Article  Google Scholar 

  67. Leydet-Quilici H, Le Corroller T, Bouvier C, Giorgi R, Argenson JN, Champsaur P, et al. Advanced hip osteoarthritis: magnetic resonance imaging aspects and histopathology correlations. Osteoarthr Cartil. 2010;18:1429–35.

    Article  CAS  PubMed  Google Scholar 

  68. Felson DT, McLaughlin S, Goggins J, LaValley MP, Gale ME, Totterman S, et al. Bone marrow edema and its relation to progression of knee osteoarthritis. Ann Intern Med. 2003;139:330–6.

    Article  PubMed  Google Scholar 

  69. Hunter DJ, Zhang Y, Niu J, Goggins J, Amin S, LaValley MP, et al. Increase in bone marrow lesions associated with cartilage loss: a longitudinal magnetic resonance imaging study of knee osteoarthritis. Arthritis Rheum. 2006;54:1529–35.

    Article  PubMed  Google Scholar 

  70. Lo GH, Hunter DJ, Nevitt M, Lynch J, McAlindon TE. Strong association of MRI meniscal derangement and bone marrow lesions in knee osteoarthritis: data from the osteoarthritis initiative. Osteoarthr Cartil. 2009;17:743–7.

    Article  CAS  PubMed  Google Scholar 

  71. Crema MD, Roemer FW, Zhu Y, Marra MD, Niu J, Zhang Y, et al. Subchondral cystlike lesions develop longitudinally in areas of bone marrow edema-like lesions in patients with or at risk for knee osteoarthritis: detection with MR imaging—the MOST study. Radiology. 2010;256:855–62.

    Article  PubMed  PubMed Central  Google Scholar 

  72. Radin EL, Paul IL, Tolkoff MJ. Subchondral bone changes in patients with early degenerative joint disease. Arthritis Rheum. 1970;13:400–5.

    Article  CAS  PubMed  Google Scholar 

  73. Schett G, Zwerina J, David JP. The role of Wnt proteins in arthritis. Nat Clin Pract Rheumatol. 2008;4:473–80.

    Article  CAS  PubMed  Google Scholar 

  74. Zhu M, Tang D, Wu Q, Hao S, Chen M, Xie C, et al. Activation of beta-catenin signaling in articular chondrocytes leads to osteoarthritis-like phenotype in adult beta-catenin conditional activation mice. J Bone Miner Res. 2009;24:12–21.

    Article  CAS  PubMed  Google Scholar 

  75. Funck-Brentano T, Bouaziz W, Marty C, Geoffroy V, Hay E, Cohen-Solal M. Dkk-1-mediated inhibition of Wnt signaling in bone ameliorates osteoarthritis in mice. Arthritis Rheumatol. 2014;66:3028–39.

    Article  CAS  PubMed  Google Scholar 

  76. Dequeker J, Aerssens J, Luyten FP. Osteoarthritis and osteoporosis: clinical and research evidence of inverse relationship. Aging Clin Exp Res. 2003;15:426–39.

    Article  PubMed  Google Scholar 

  77. Hochberg MC, Lethbridge-Cejku M, Tobin JD. Bone mineral density and osteoarthritis: data from the Baltimore Longitudinal Study of Aging. Osteoarthr Cartil. 2004;12A:S45–8.

    Article  Google Scholar 

  78. Herrero-Beaumont G, Roman-Blas JA, Largo R, Berenbaum F, Castañeda S. Bone mineral density and joint cartilage: four clinical settings of a complex relationship in osteoarthritis. Ann Rheum Dis. 2011;70:1523–5.

    Article  PubMed  Google Scholar 

  79. Karsdal MA, Bay-Jensen AC, Lories RJ, Abramson S, Spector T, Pastoureau P, et al. The coupling of bone and cartilage turnover in osteoarthritis: opportunities for bone antiresorptives and anabolics as potential treatments? Ann Rheum Dis. 2014;73:336–48.

    Article  CAS  PubMed  Google Scholar 

  80. Funck-Brentano T, Cohen-Solal M. Subchondral bone and osteoarthritis. Curr Opin Rheumatol. 2015;27:420–6.

    Article  PubMed  Google Scholar 

  81. Poulet B, Staines KA. New developments in osteoarthritis and cartilage biology. Curr Opin Pharmacol. 2016;28:8–13.

    Article  CAS  PubMed  Google Scholar 

  82. Clark JM, Huber JD. The structure of the human subchondral plate. J Bone Joint Surg Br. 1990;72:866–73.

    Article  CAS  PubMed  Google Scholar 

  83. Zhang L, Gardiner BS, Smith DW, Pivonka P, Grodzinsky AJ. On the role of diffusible binding partners in modulating the transport and concentration of proteins in tissues. J Theor Biol. 2010;263:20–9.

    Article  CAS  PubMed  Google Scholar 

  84. Zhang LZ, Zheng HA, Jiang Y, Tu YH, Jiang PH, Yang AL. Mechanical and biologic link between cartilage and subchondral bone in osteoarthritis. Arthritis Care Res (Hoboken). 2012;64:960–7.

    CAS  Google Scholar 

  85. Findlay DM, Atkins GJ. Osteoblast-chondrocyte interactions in osteoarthritis. Curr Osteoporos Rep. 2014;12:127–34.

    Article  PubMed  PubMed Central  Google Scholar 

  86. Couchourel D, Aubry I, Delalandre A, Lavigne M, Martel-Pelletier J, Pelletier JP, et al. Altered mineralization of human osteoarthritic osteoblasts is attributable to abnormal type 1 collagen production. Arthritis Rheum. 2009;60:1438–50.

    Article  PubMed  PubMed Central  Google Scholar 

  87. Kumarasinghe DD, Sullivan T, Kuliwaba JS, Fazzalari NL, Atkins GJ. Evidence for the dysregulated expression of TWIST1, TGFβ1, and SMAD3 in differentiating osteoblasts from primary hip osteoarthritis patients. Osteoarthr Cartil. 2012;20:1357–66.

    Article  CAS  PubMed  Google Scholar 

  88. Truong L-H, Kuliwaba JS, Tsangari H, Fazzalari NL. Differential gene expression of bone anabolic factors and trabecular bone architectural changes in the proximal femoral shaft of primary hip osteoarthritis patients. Arthrit Res Ther. 2006;8:R188.

    Article  CAS  Google Scholar 

  89. Chan TF, Couchourel D, Abed E, Delalandre A, Duval N, Lajeunesse D. Elevated Dickkopf-2 levels contribute to the abnormal phenotype of human osteoarthritic osteoblasts. J Bone Miner Res. 2011;26:1399–410.

    Article  CAS  PubMed  Google Scholar 

  90. Sanchez C, Deberg MA, Piccardi N, Msika P, Reginster JYL, Henrotin YE. Osteoblasts from the sclerotic subchondral bone downregulate aggrecan but upregulate metalloproteinases expression by chondrocytes. This effect is mimicked by interleukin-6, -1β and oncostatin M pre-treated non-sclerotic osteoblasts. Osteoarthr Cartil. 2005;13:979–87.

    Article  CAS  PubMed  Google Scholar 

  91. Sanchez C, DebergMA PN, Msika P, Reginster JY, Henrotin Y. Subchondral bone osteoblasts induce phenotypic changes in human osteoarthritic chondrocytes. Osteoarthr Cartil. 2005;13:988–97.

    Article  CAS  PubMed  Google Scholar 

  92. Villalvilla A, Gómez R, Largo R, Herrero-Beaumont G. Lipid transport and metabolism in healthy and osteoarthritic cartilage. Int J Mol Sci. 2013;14:20793–808.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  93. Gosset M, Berenbaum F, Salvat C, Sautet A, Pigenet A, Tahiri K, et al. Crucial role of visfatin/pre-B cell colonyenhancing factor in matrix degradation and prostaglandin E2 synthesis in chondrocytes: possible influence on osteoarthritis. Arthritis Rheum. 2008;58:1399–409.

    Article  CAS  PubMed  Google Scholar 

  94. Griffin TM, Huebner JL, Kraus VB, Guilak F. Extreme obesity due to impaired leptin signaling in mice does not cause knee osteoarthritis. Arthritis Rheum. 2009;60:2935–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Mutabaruka MS, Aoulad Aissa M, Delalandre A, Lavigne M, Lajeunesse D. Local leptin production in osteoarthritis subchondral osteoblasts may be responsible for their abnormal phenotypic expression. Arthritis Res Ther. 2010;12:R20.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  96. Davies-Tuck ML, Hanna F, Davis SR, Bell RJ, Davison SL, Wluka AE, et al. Total cholesterol and triglycerides are associated with the development of new bone marrow lesions in asymptomatic middle-aged women—a prospective cohort study. Arthritis Res Ther. 2009;11:R181.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  97. Blom AB, Brockbank SM, van Lent PL, van Beuningen HM, Geurts J, Takahashi N, et al. Involvement of the Wnt signaling pathway in experimental and human osteoarthritis: prominent role of Wnt-induced signaling protein 1. Arthritis Rheum. 2009;60:501–12.

    Article  CAS  PubMed  Google Scholar 

  98. Papathanasiou I, Malizos KN, Tsezou A. Low-density lipoprotein receptor-related protein 5 (LRP5) expression in human osteoarthritic chondrocytes. J Orthop Res. 2010;28:348–53.

    CAS  PubMed  Google Scholar 

  99. Kumarasinghe DD, Perilli E, Tsangari H, Truong L, Kuliwaba JS, Hopwood B, et al. Critical molecular regulators, histomorphometric indices and their correlations in the trabecular bone in primary hip osteoarthritis. Osteoarthr Cartil. 2010;18:1337–44.

    Article  CAS  PubMed  Google Scholar 

  100. Guevremont M, Martel-Pelletier J, Massicotte F, Tardif G, Pelletier JP, Ranger P, et al. Human adult chondrocytes express hepatocyte growth factor (HGF) isoforms but not HgF: potential implication of osteoblasts on the presence of HGF in cartilage. J Bone Miner Res. 2003;18:1073–81.

    Article  CAS  PubMed  Google Scholar 

  101. Walsh DA, Bonnet CS, Turner EL, Wilson D, Situ M, McWilliams DF. Angiogenesis in the synovium and at the osteochondral junction in osteoarthritis. Osteoarthr Cartil. 2007;15:743–51.

    Article  CAS  PubMed  Google Scholar 

  102. Shibakawa A, Yudoh K, Masuko-Hongo K, Kato T, Nishioka K, Nakamura H. The role of subchondral bone resorption pits in osteoarthritis: MMP production by cells derived from bone marrow. Osteoarthr Cartil. 2005;13:679–87.

    Article  CAS  PubMed  Google Scholar 

  103. Suri S, Gill SE, de Massena Camin S, Wilson D, DF MW, Walsh DA. Neurovascular invasion at the osteochondral junction and in osteophytes in osteoarthritis. Ann Rheum Dis. 2007;66:1423–8.

    Article  PubMed  PubMed Central  Google Scholar 

  104. Martín-Millán M, Castañeda S. Estrogens, osteoarthritis and inflammation. Joint Bone Spine. 2013;80:368–73.

    Article  PubMed  CAS  Google Scholar 

  105. Berenbaum F. Osteoarthritis as an inflammatory disease (osteoarthritis is not osteoarthrosis!). Osteoarthr Cartil. 2013;21:16–21.

    Article  CAS  PubMed  Google Scholar 

  106. Roemer FW, Guermazi A, Felson DT, Niu J, Nevitt MC, Crema MD, et al. Presence of MRI-detected joint effusion and synovitis increases the risk of cartilage loss in knees without osteoarthritis at 30-month follow-up: the MOST study. Ann Rheum Dis. 2011;70:1804–9.

    Article  PubMed  PubMed Central  Google Scholar 

  107. Ayral X, Pickering EH, Woodworth TG, Mackillop N, Dougados M. Synovitis: a potential predictive factor of structural progression of medial tibiofemoral knee osteoarthritis—results of a 1 year longitudinal arthroscopic study in 422 patients. Osteoarthr Cartil. 2005;13:361–7.

    Article  CAS  PubMed  Google Scholar 

  108. Pearle AD, Scanzello CR, George S, Mandl LA, DiCarlo EF, Peterson M, et al. Elevated high-sensitivity C-reactive protein levels are associated with local inflammatory findings in patients with osteoarthritis. Osteoarthr Cartil. 2007;15:516–23.

    Article  CAS  PubMed  Google Scholar 

  109. Kapoor M, Martel-Pelletier J, Lajeunesse D, Pelletier JP, Fahmi H. Role of proinflammatory cytokines in the pathophysiology of osteoarthritis. Nat Rev Rheumatol. 2011;7:33–42.

    Article  CAS  PubMed  Google Scholar 

  110. Blom AB, van Lent PLEM, Holthuysen AEM, van der Kraan PM, Roth J, van Rooijen N, et al. Synovial lining macrophages mediate osteophyte formation during experimental osteoarthritis. Osteoarthr Cartil. 2004;12:627–35.

    Article  PubMed  Google Scholar 

  111. van Lent PL, Blom AB, van der Kraan P, Holthuysen AE, Vitters E, van Rooijen N, et al. Crucial role of synovial lining macrophages in the promotion of transforming growth factor β-mediated osteophyte formation. Arthritis Rheum. 2004;50:103–11.

    Article  PubMed  CAS  Google Scholar 

  112. Suurmond J, Dorjée AL, Boon MR, Knol EF, Huizinga TWJ, Toes REM, et al. Mast cells are the main interleukin 17-positive cells in anticitrullinated protein antibody-positive and -negative rheumatoid arthritis and osteoarthritis synovium. Arthritis Res Ther. 2011;13:R150.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Gordon S. Pattern recognition receptors: doubling up for the innate immune response. Cell. 2002;111:927–30.

    Article  CAS  PubMed  Google Scholar 

  114. Kawai T, Akira S. The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat Immunol. 2010;11:373–84.

    Article  CAS  PubMed  Google Scholar 

  115. Gómez R, Villalvilla A, Largo R, Gualillo O, Herrero-Beaumont G. TLR4 signalling in osteoarthritis—finding targets for candidate DMOADs. Nat Rev Rheumatol. 2015;11:159–70.

    Article  PubMed  CAS  Google Scholar 

  116. Kim HA, Cho M-L, Choi HY, Yoon CS, Jhun JY, Oh HJ, et al. The catabolic pathway mediated by toll-like receptors in human osteoarthritic chondrocytes. Arthritis Rheum. 2006;54:2152–63.

    Article  CAS  PubMed  Google Scholar 

  117. Scanzello CR, Plaas A, Crow MK. Innate immune system activation in osteoarthritis: is osteoarthritis a chronic wound? Curr Opin Rheumatol. 2008;20:565–72.

    Article  CAS  PubMed  Google Scholar 

  118. van Lent PLEM, Blom AB, Schelbergen RFP, Slöetjes A, Lafeber FPJG, Lems WF, et al. Active involvement of alarmins S100A8 and S100A9 in the regulation of synovial activation and joint destruction during mouse and human osteoarthritis. Arthritis Rheum. 2012;64:1466–76.

    Article  PubMed  CAS  Google Scholar 

  119. Jung YO, Cho ML, Lee SY, Oh HJ, Park JS, Park MK, et al. Synergism of Toll-like receptor 2 (TLR2), TLR4, and TLR6 ligation on the production of tumor necrosis factor (TNF)-α in a spontaneous arthritis animal model of interleukin (IL)-1 receptor antagonist-deficient mice. Immunol Lett. 2009;123:138–43.

    Article  CAS  PubMed  Google Scholar 

  120. Rosenthal AK. Crystals, inflammation, and osteoarthritis. Curr Opin Rheumatol. 2011;23:170–3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. MacMullan P, McMahon G, McCarthy G. Detection of basic calcium phosphate crystals in osteoarthritis. Joint Bone Spine. 2011;78:358–63.

    Article  CAS  PubMed  Google Scholar 

  122. Gibilisco P, Schumacher HJ, Hollander J, Soper K. Synovial fluid crystals in osteoarthritis. Arthritis Rheum. 1984;28:511–5.

    Article  Google Scholar 

  123. Fuerst M, Bertrand J, Lammers L, Dreier R, Echtermeyer F, Nitschke Y, et al. Calcification of articular cartilage in human osteoarthritis. Arthritis Rheum. 2009;60:2694–703.

    Article  CAS  PubMed  Google Scholar 

  124. Zhuo Q, Yang W, Chen J, Wang Y. Metabolic syndrome meets osteoarthritis. Nat Rev Rheumatol. 2012;8:729–37.

    Article  CAS  PubMed  Google Scholar 

  125. Berenbaum F, Eymard F, Houard X. Osteoarthritis, inflammation and obesity. Curr Opin Rheumatol. 2013;25:114–8.

    Article  CAS  PubMed  Google Scholar 

  126. You T, Nicklas BJ. Chronic inflammation: role of adipose tissue and modulation by weight loss. Curr Diabetes Rev. 2006;2:29–37.

    Article  PubMed  Google Scholar 

  127. Haseeb A, Haqqi TM. Immunopathogenesis of osteoarthritis. Clin Immunol. 2013;146:185–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. de Boer TN, van Spil WE, Huisman AM, Polak AA, Bijlsma JW, Lafeber FP, et al. Serum adipokines in osteoarthritis; comparison with controls and relationship with local parameters of synovial inflammation and cartilage damage. Osteoarthr Cartil. 2012;20:846–53.

    Article  PubMed  Google Scholar 

  129. Malemud CJ. Biologic basis of osteoarthritis: state of the evidence. Curr Opin Rheumatol. 2015;27:289–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Robinson WH, Lepus CM, Wang Q, Raghu H, Mao R, Lindstrom TM, Sokolove J. Low-grade inflammation as a key mediator of the pathogenesis of osteoarthritis. Nat Rev Rheumatol. 2016;12:580–92.

    Article  CAS  PubMed  Google Scholar 

  131. Dumond H, Presle N, Terlain B, Mainard D, Loeuille D, Netter P, et al. Evidence for a key role of leptin in osteoarthritis. Arthritis Rheum. 2003;48:3118–29.

    Article  CAS  PubMed  Google Scholar 

  132. Francin PJ, Abot A, Guillaume C, Moulin D, Bianchi A, Gegout-Pottie P, et al. Association between adiponectin and cartilage degradation in human osteoarthritis. Osteoarthr Cartil. 2014;22:519–26.

    Article  PubMed  Google Scholar 

  133. Presle N, Pottie P, Dumond H, Guillaume C, Lapicque F, Pallu S, et al. Differential distribution of adipokines between serum and synovial fluid in patients with osteoarthritis. Contribution of joint tissues to their articular production. Osteoarthr Cartil. 2006;14:690–5.

    Article  CAS  PubMed  Google Scholar 

  134. Sokolove J, Lepus CM. Role of inflammation in the pathogenesis of osteoarthritis: latest findings and interpretations. Ther Adv Musculoskeletal Dis. 2013;5:77–94.

    Article  CAS  Google Scholar 

  135. Rasheed Z, Akhtar N, Haqqi TM. Advanced glycation end products induce the expression of interleukin-6 and interleukin-8 by receptor for advanced glycation end productmediated activation of mitogen-activated protein kinases and nuclear factor-B in human osteoarthritis chondrocytes. Rheumatology (Oxford). 2010;50:838–51.

    Article  CAS  Google Scholar 

  136. Lotz M, Loeser RF. Effects of aging on articular cartilage homeostasis. Bone. 2012;51:241–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Guilak F. Biomechanical factors in osteoarthritis. Best Pract Res Clin Rheumatol. 2011;25:815–23.

    Article  PubMed  PubMed Central  Google Scholar 

  138. Berenbaum F. Signaling transduction: target in osteoarthritis. Curr Opin Rheumatol. 2004;16:616–22.

    Article  PubMed  Google Scholar 

  139. Englund M. The role of the meniscus in osteoarthritis genesis. Med Clin North Am. 2009;93:37–43.

    Article  PubMed  Google Scholar 

  140. Pauli C, Grogan SP, Patil S, Otsuki S, Hasegawa A, Koziol J, et al. Macroscopic and histopathologic analysis of human knee menisci in aging and osteoarthritis. Osteoarthr Cartil. 2011;19:1132–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Sun Y, Mauerhan DR, Kneisl JS, Norton HJ, Zinchenko N, Ingram J, et al. Histological examination of collagen and proteoglycan changes in osteoarthritic menisci. Open Rheumatol J. 2012;6:24–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Sun Y, Mauerhan DR, Heneycutt PR, Kneisl JS, Norton HJ, Zinchenko N, et al. Calcium deposition in osteoarthritic menisci and meniscal cell culture. Arthritis Res Ther. 2010;12:R56.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  143. Lee DH, Lee BS, Kim JM, Yang KS, Cha EJ, Park JH, Bin SI. Predictors of degenerative medial meniscus extrusion: radial component and knee osteoarthritis. Knee Surg Sports Traumatol Arthrosc. 2011;19:222–9.

    Article  PubMed  Google Scholar 

  144. Englund M, Roemer FW, Hayashi D, Crema MD, Guermazi A. Meniscus pathology, osteoarthritis and the treatment controversy. Nat Rev Rheumatol. 2012;8:412–9.

    Article  CAS  PubMed  Google Scholar 

  145. Roos EM, Herzog W, Block JA, Bennell KL. Muscle weakness, afferent sensory dysfunction and exercise in knee osteoarthritis. Nat Rev Rheumatol. 2011;7:57–63.

    Article  PubMed  Google Scholar 

  146. Segal NA, Torner JC, Felson D, Niu J, Sharma L, Lewis CE, et al. Effect of thigh strength on incident radiographic and symptomatic knee osteoarthritis in a longitudinal cohort. Arthritis Rheum. 2009;61:1210–7.

    Article  PubMed  PubMed Central  Google Scholar 

  147. Distel E, Cadoudal T, Durant S, Poignard A, Chevalier X, Benelli C. The infrapatellar fat pad in knee osteoarthritis: an important source of interleukin-6 and its soluble receptor. Arthritis Rheum. 2009;60:3374–7.

    Article  CAS  PubMed  Google Scholar 

  148. Gandhi R, Takahashi M, Virtanen C, Syed K, Davey JR, Mahomed NN. Microarray analysis of the infrapatellar fat pad in knee osteoarthritis: relationship with joint inflammation. J Rheumatol. 2011;38:1966–72.

    Article  CAS  PubMed  Google Scholar 

  149. Clockaerts S, Bastiaansen-Jenniskens YM, Runhaar J, Van Osch GJ, Van Offel JF, Verhaar JA, et al. The infrapatellar fat pad should be considered as an active osteoarthritic joint tissue: a narrative review. Osteoarthr Cartil. 2010;18:876–82.

    Article  CAS  PubMed  Google Scholar 

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Castañeda, S., Vicente, E.F. Osteoarthritis: More than Cartilage Degeneration. Clinic Rev Bone Miner Metab 15, 69–81 (2017). https://doi.org/10.1007/s12018-017-9228-6

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