Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Biological aspects of early osteoarthritis

Abstract

Purpose

Early OA primarily affects articular cartilage and involves the entire joint, including the subchondral bone, synovial membrane, menisci and periarticular structures. The aim of this review is to highlight the molecular basis and histopathological features of early OA.

Methods

Selective review of literature.

Results

Risk factors for developing early OA include, but are not limited to, a genetic predisposition, mechanical factors such as axial malalignment, and aging. In early OA, the articular cartilage surface is progressively becoming discontinuous, showing fibrillation and vertical fissures that extend not deeper than into the mid-zone of the articular cartilage, reflective of OARSI grades 1.0–3.0. Early changes in the subchondral bone comprise a progressive increase in subchondral plate and subarticular spongiosa thickness. Early OA affects not only the articular cartilage and the subchondral bone but also other structures of the joint, such as the menisci, the synovial membrane, the joint capsule, ligaments, muscles and the infrapatellar fat pad. Genetic markers or marker combinations may become useful in the future to identify early OA and patients at risk.

Conclusion

The high socioeconomic impact of OA suggests that a better insight into the mechanisms of early OA may be a key to develop more targeted reconstructive therapies at this first stage of the disease.

Level of evidence

Systematic review, Level II.

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

References

  1. 1.

    Aaboe J, Bliddal H, Messier SP, Alkjaer T, Henriksen M (2011) Effects of an intensive weight loss program on knee joint loading in obese adults with knee osteoarthritis. Osteoarthritis Cartilage 19(7):822–828

  2. 2.

    Aagaard H, Verdonk R (1999) Function of the normal meniscus and consequences of meniscal resection. Scand J Med Sci Sports 9(3):134–140

  3. 3.

    Adams ME, Brandt KD (1991) Hypertrophic repair of canine articular cartilage in osteoarthritis after anterior cruciate ligament transection. J Rheumatol 18(3):428–435

  4. 4.

    Aigner T, Cook JL, Gerwin N, Glasson SS, Laverty S, Little CB, McIlwraith W, Kraus VB (2010) Histopathology atlas of animal model systems—overview of guiding principles. Osteoarthritis Cartilage 18(Suppl 3):S2–S6

  5. 5.

    Aigner T, Soder S, Gebhard PM, McAlinden A, Haag J (2007) Mechanisms of disease: role of chondrocytes in the pathogenesis of osteoarthritis–structure, chaos and senescence. Nat Clin Pract Rheumatol 3(7):391–399

  6. 6.

    Ameye LG, Young MF (2006) Animal models of osteoarthritis: lessons learned while seeking the “Holy Grail”. Curr Opin Rheumatol 18(5):537–547

  7. 7.

    Aoki H, Nagao Y, Ishii S, Masuda T, Beppu M (2010) Acetabular and proximal femoral alignment in patients with osteoarthritis of the dysplastic hip and its influence on the progression of disease. J Bone Joint Surg Br 92(12):1703–1709

  8. 8.

    Attur MG, Dave M, Akamatsu M, Katoh M, Amin AR (2002) Osteoarthritis or osteoarthrosis: the definition of inflammation becomes a semantic issue in the genomic era of molecular medicine. Osteoarthritis Cartilage 10(1):1–4

  9. 9.

    Attur MG, Dave MN, Tsunoyama K, Akamatsu M, Kobori M, Miki J, Abramson SB, Katoh M, Amin AR (2002) “A system biology” approach to bioinformatics and functional genomics in complex human diseases: arthritis. Curr Issues Mol Biol 4(4):129–146

  10. 10.

    Becerra J, Andrades JA, Guerado E, Zamora-Navas P, Lopez-Puertas JM, Reddi AH (2011) Articular cartilage: structure and regeneration. Tissue Eng Part B Rev 16(6):617–627

  11. 11.

    Bellido M, Lugo L, Roman-Blas JA, Castaneda S, Caeiro JR, Dapia S, Calvo E, Largo R, Herrero-Beaumont G (2010) Subchondral bone microstructural damage by increased remodelling aggravates experimental osteoarthritis preceded by osteoporosis. Arthritis Res Ther 12(4):R152

  12. 12.

    Bellido M, Lugo L, Roman-Blas JA, Castaneda S, Calvo E, Largo R, Herrero-Beaumont G (2011) Improving subchondral bone integrity reduces progression of cartilage damage in experimental osteoarthritis preceded by osteoporosis. Osteoarthritis Cartilage 19(10):1228–1236

  13. 13.

    Bertrand J, Cromme C, Umlauf D, Frank S, Pap T (2010) Molecular mechanisms of cartilage remodelling in osteoarthritis. Int J Biochem Cell Biol 42(10):1594–1601

  14. 14.

    Beyer C, Schett G (2010) Pharmacotherapy: concepts of pathogenesis and emerging treatments. Novel targets in bone and cartilage. Best Pract Res Clin Rheumatol 24(4):489–496

  15. 15.

    Bijkerk C, Houwing-Duistermaat JJ, Valkenburg HA, Meulenbelt I, Hofman A, Breedveld FC, Pols HA, van Duijn CM, Slagboom PE (1999) Heritabilities of radiologic osteoarthritis in peripheral joints and of disc degeneration of the spine. Arthritis Rheum 42(8):1729–1735

  16. 16.

    Bijlsma JW, Berenbaum F, Lafeber FP (2011) Osteoarthritis: an update with relevance for clinical practice. Lancet 377(9783):2115–2126

  17. 17.

    Blanco FJ, Guitian R, Vazquez-Martul E, de Toro FJ, Galdo F (1998) Osteoarthritis chondrocytes die by apoptosis. A possible pathway for osteoarthritis pathology. Arthritis Rheum 41(2):284–289

  18. 18.

    Bliddal H, Christensen R (2009) The treatment and prevention of knee osteoarthritis: a tool for clinical decision-making. Expert Opin Pharmacother 10(11):1793–1804

  19. 19.

    Bliddal H, Leeds AR, Stigsgaard L, Astrup A, Christensen R (2011) Weight loss as treatment for knee osteoarthritis symptoms in obese patients: 1-year results from a randomised controlled trial. Ann Rheum Dis 70(10):1798–1803

  20. 20.

    Borzi RM, Mazzetti I, Cattini L, Uguccioni M, Baggiolini M, Facchini A (2000) Human chondrocytes express functional chemokine receptors and release matrix-degrading enzymes in response to C-X-C and C–C chemokines. Arthritis Rheum 43(8):1734–1741

  21. 21.

    Borzi RM, Mazzetti I, Macor S, Silvestri T, Bassi A, Cattini L, Facchini A (1999) Flow cytometric analysis of intracellular chemokines in chondrocytes in vivo: constitutive expression and enhancement in osteoarthritis and rheumatoid arthritis. FEBS Lett 455(3):238–242

  22. 22.

    Borzi RM, Mazzetti I, Magagnoli G, Paoletti S, Uguccioni M, Gatti R, Orlandini G, Cattini L, Facchini A (2002) Growth-related oncogene alpha induction of apoptosis in osteoarthritis chondrocytes. Arthritis Rheum 46(12):3201–3211

  23. 23.

    Borzi RM, Mazzetti I, Marcu KB, Facchini A (2004) Chemokines in cartilage degradation. Clin Orthop Relat Res 427(Suppl):S53–S61

  24. 24.

    Botter SM, van Osch GJ, Clockaerts S, Waarsing JH, Weinans H, van Leeuwen JP (2011) Osteoarthritis induction leads to early and temporal subchondral plate porosity in the tibial plateau of mice: An in vivo micro CT study. Arthritis Rheum. doi:10.1002/art.30307

  25. 25.

    Brandt KD (1998) The importance of nonpharmacologic approaches in management of osteoarthritis. Am J Med 105(1B):39S–44S

  26. 26.

    Brandt KD (2000) The role of analgesics in the management of osteoarthritis pain. Am J Ther 7(2):75–90

  27. 27.

    Brandt KD, Dieppe P, Radin EL (2009) Commentary: is it useful to subset “primary” osteoarthritis? A critique based on evidence regarding the etiopathogenesis of osteoarthritis. Semin Arthritis Rheum 39(2):81–95

  28. 28.

    Brouwer GM, van Tol AW, Bergink AP, Belo JN, Bernsen RM, Reijman M, Pols HA, Bierma-Zeinstra SM (2007) Association between valgus and varus alignment and the development and progression of radiographic osteoarthritis of the knee. Arthritis Rheum 56(4):1204–1211

  29. 29.

    Buckland-Wright C (2004) Subchondral bone changes in hand and knee osteoarthritis detected by radiography. Osteoarthritis Cartilage 12(Suppl A):S10–S19

  30. 30.

    Buckwalter JA, Mankin HJ (1998) Articular cartilage: degeneration and osteoarthritis, repair, regeneration, and transplantation. Instr Course Lect 47:487–504

  31. 31.

    Buckwalter JA, Mankin HJ, Grodzinsky AJ (2005) Articular cartilage and osteoarthritis. Instr Course Lect 54:465–480

  32. 32.

    Bullough PG (1998) Disorders of bone, cartilage and connective tissue. Osteoarthritis and related disorders. Patholohy. In: Klippel JH, Huston DP (ed) Rheumatology, 2nd edn. Mosby, London, pp 8.1–8.8

  33. 33.

    Bullough PG (2004) The role of joint architecture in the etiology of arthritis. Osteoarthr Cartil 12(Suppl A):S2–S9

  34. 34.

    Burr DB, Radin EL (2003) Microfractures and microcracks in subchondral bone: are they relevant to osteoarthrosis? Rheum Dis Clin North Am 29(4):675–685

  35. 35.

    Carlson CS, Loeser RF, Jayo MJ, Weaver DS, Adams MR, Jerome CP (1994) Osteoarthritis in cynomolgus macaques: a primate model of naturally occurring disease. J Orthop Res 12(3):331–339

  36. 36.

    Carlson CS, Loeser RF, Purser CB, Gardin JF, Jerome CP (1996) Osteoarthritis in cynomolgus macaques. III: Effects of age, gender, and subchondral bone thickness on the severity of disease. J Bone Miner Res 11(9):1209–1217

  37. 37.

    Cerejo R, Dunlop DD, Cahue S, Channin D, Song J, Sharma L (2002) The influence of alignment on risk of knee osteoarthritis progression according to baseline stage of disease. Arthritis Rheum 46(10):2632–2636

  38. 38.

    Chang DG, Iverson EP, Schinagl RM, Sonoda M, Amiel D, Coutts RD, Sah RL (1997) Quantitation and localization of cartilage degeneration following the induction of osteoarthritis in the rabbit knee. Osteoarthritis Cartilage 5(5):357–372

  39. 39.

    Chen MI, Branch TP, Hutton WC (1996) Is it important to secure the horns during lateral meniscal transplantation? A cadaveric study. Arthroscopy 12(2):174–181

  40. 40.

    Chiba K, Ito M, Osaki M, Uetani M, Shindo H (2011) In vivo structural analysis of subchondral trabecular bone in osteoarthritis of the hip using multi-detector row CT. Osteoarthritis Cartilage 19(2):180–185

  41. 41.

    Chiba K, Uetani M, Kido Y, Ito M, Okazaki N, Taguchi K, Shindo H (2011) Osteoporotic changes of subchondral trabecular bone in osteoarthritis of the knee: a 3-T MRI study. Osteoporos Int [Epub ahead of print]

  42. 42.

    Chitnavis J, Sinsheimer JS, Clipsham K, Loughlin J, Sykes B, Burge PD, Carr AJ (1997) Genetic influences in end-stage osteoarthritis. Sibling risks of hip and knee replacement for idiopathic osteoarthritis. J Bone Joint Surg Br 79(4):660–664

  43. 43.

    Chockalingam PS, Varadarajan U, Sheldon R, Fortier E, LaVallie ER, Morris EA, Yaworsky PJ, Majumdar MK (2007) Involvement of protein kinase Czeta in interleukin-1beta induction of ADAMTS-4 and type 2 nitric oxide synthase via NF-kappaB signaling in primary human osteoarthritic chondrocytes. Arthritis Rheum 56(12):4074–4083

  44. 44.

    Christensen R, Bartels EM, Astrup A, Bliddal H (2007) Effect of weight reduction in obese patients diagnosed with knee osteoarthritis: a systematic review and meta-analysis. Ann Rheum Dis 66(4):433–439

  45. 45.

    Cicuttini F, Wluka A, Hankin J, Wang Y (2004) Longitudinal study of the relationship between knee angle and tibiofemoral cartilage volume in subjects with knee osteoarthritis. Rheumatology (Oxford) 43(3):321–324

  46. 46.

    Clark JM (1990) The structure of vascular channels in the subchondral plate. J Anat 171:105–115

  47. 47.

    Clockaerts S, Bastiaansen-Jenniskens YM, Runhaar J, Van Osch GJ, Van Offel JF, Verhaar JA, De Clerck LS, Somville J (2010) The infrapatellar fat pad should be considered as an active osteoarthritic joint tissue: a narrative review. Osteoarthritis Cartilage 18(7):876–882

  48. 48.

    Crema MD, Guermazi A, Li L, Nogueira-Barbosa MH, Marra MD, Roemer FW, Eckstein F, Le Graverand MP, Wyman BT, Hunter DJ (2009) The association of prevalent medial meniscal pathology with cartilage loss in the medial tibiofemoral compartment over a 2-year period. Osteoarthritis Cartilage 18(3):336–343

  49. 49.

    Cucchiarini M, Orth P, Madry H (2011) Gene therapy for cartilage repair. Cartilage 2(3):201–225

  50. 50.

    Daans M, Luyten FP, Lories RJ (2011) GDF5 deficiency in mice is associated with instability-driven joint damage, gait and subchondral bone changes. Ann Rheum Dis 70(1):208–213

  51. 51.

    De Ceuninck F, Dassencourt L, Anract P (2004) The inflammatory side of human chondrocytes unveiled by antibody microarrays. Biochem Biophys Res Commun 323(3):960–969

  52. 52.

    Dejour H, Walch G, Deschamps G, Chambat P (1987) Arthrosis of the knee in chronic anterior laxity. Rev Chir Orthop Reparatrice Appar Mot 73(3):157–170

  53. 53.

    Dieppe P, Cushnaghan J, Young P, Kirwan J (1993) Prediction of the progression of joint space narrowing in osteoarthritis of the knee by bone scintigraphy. Ann Rheum Dis 52(8):557–563

  54. 54.

    Distel E, Cadoudal T, Durant S, Poignard A, Chevalier X, Benelli C (2009) The infrapatellar fat pad in knee osteoarthritis: an important source of interleukin-6 and its soluble receptor. Arthritis Rheum 60(11):3374–3377

  55. 55.

    Drissi H, Zuscik M, Rosier R, O’Keefe R (2005) Transcriptional regulation of chondrocyte maturation: potential involvement of transcription factors in OA pathogenesis. Mol Aspects Med 26(3):169–179

  56. 56.

    Echtermeyer F, Bertrand J, Dreier R, Meinecke I, Neugebauer K, Fuerst M, Lee YJ, Song YW, Herzog C, Theilmeier G, Pap T (2009) Syndecan-4 regulates ADAMTS-5 activation and cartilage breakdown in osteoarthritis. Nat Med 15(9):1072–1076

  57. 57.

    Englund M, Guermazi A, Lohmander LS (2009) The meniscus in knee osteoarthritis. Rheum Dis Clin North Am 35(3):579–590

  58. 58.

    Englund M, Guermazi A, Lohmander SL (2009) The role of the meniscus in knee osteoarthritis: a cause or consequence? Radiol Clin North Am 47(4):703–712

  59. 59.

    Englund M, Guermazi A, Roemer FW, Aliabadi P, Yang M, Lewis CE, Torner J, Nevitt MC, Sack B, Felson DT (2009) Meniscal tear in knees without surgery and the development of radiographic osteoarthritis among middle-aged and elderly persons: The Multicenter Osteoarthritis Study. Arthritis Rheum 60(3):831–839

  60. 60.

    Englund M, Lohmander LS (2004) Risk factors for symptomatic knee osteoarthritis fifteen to twenty-two years after meniscectomy. Arthritis Rheum 50(9):2811–2819

  61. 61.

    Fahmy NR, Williams EA, Noble J (1983) Meniscal pathology and osteoarthritis of the knee. J Bone Joint Surg Br 65(1):24–28

  62. 62.

    Feeley BT, Gallo RA, Sherman S, Williams RJ (2010) Management of osteoarthritis of the knee in the active patient. J Am Acad Orthop Surg 18(7):406–416

  63. 63.

    Felson DT, Couropmitree NN, Chaisson CE, Hannan MT, Zhang Y, McAlindon TE, LaValley M, Levy D, Myers RH (1998) Evidence for a Mendelian gene in a segregation analysis of generalized radiographic osteoarthritis: the Framingham Study. Arthritis Rheum 41(6):1064–1071

  64. 64.

    Felson DT, Gale DR, Elon Gale M, Niu J, Hunter DJ, Goggins J, Lavalley MP (2005) Osteophytes and progression of knee osteoarthritis. Rheumatology (Oxford) 44(1):100–104

  65. 65.

    Flemming A (2010) Target identification: HIF2alpha central player in osteoarthritis. Nat Rev Drug Discov 9(7):517

  66. 66.

    Frank CB, Beveridge JE, Huebner KD, Heard BJ, Tapper JE, O’Brien EJ, Shrive NG (2011) Complete ACL/MCL deficiency induces variable degrees of instability in sheep with specific kinematic abnormalities correlating with degrees of early osteoarthritis. J Orthop Res. doi:10.1002/jor.21549

  67. 67.

    Funck-Brentano T, Cohen-Solal M (2011) Crosstalk between cartilage and bone: when bone cytokines matter. Cytokine Growth Factor Rev 22(2):91–97

  68. 68.

    Furman BD, Olson SA, Guilak F (2006) The development of posttraumatic arthritis after articular fracture. J Orthop Trauma 20(10):719–725

  69. 69.

    Gandhi R, Takahashi M, Virtanen C, Syed K, Davey JR, Mahomed NN (2011) Microarray analysis of the infrapatellar fat pad in knee osteoarthritis: relationship with joint inflammation. J Rheumatol 38(9):1966–1972

  70. 70.

    Gauci SJ, Golub SB, Tutolo L, Little CB, Sims NA, Lee ER, Mackie EJ, Fosang AJ (2008) Modulating chondrocyte hypertrophy in growth plate and osteoarthritic cartilage. J Musculoskelet Neuronal Interact 8(4):308–310

  71. 71.

    Gerwin N, Bendele AM, Glasson S, Carlson CS (2010) The OARSI histopathology initiative - recommendations for histological assessments of osteoarthritis in the rat. Osteoarthr Cartil 18(Suppl 3):S24–S34

  72. 72.

    Girkontaite I, Frischholz S, Lammi P, Wagner K, Swoboda B, Aigner T, Von der Mark K (1996) Immunolocalization of type X collagen in normal fetal and adult osteoarthritic cartilage with monoclonal antibodies. Matrix Biol 15(4):231–238

  73. 73.

    Glasson SS (2007) In vivo osteoarthritis target validation utilizing genetically-modified mice. Curr Drug Targets 8(2):367–376

  74. 74.

    Goldring MB, Goldring SR (2007) Osteoarthritis. J Cell Physiol 213(3):626–634

  75. 75.

    Goldring MB, Goldring SR (2010) Articular cartilage and subchondral bone in the pathogenesis of osteoarthritis. Ann N Y Acad Sci 1192:230–237

  76. 76.

    Goldring MB, Marcu KB (2009) Cartilage homeostasis in health and rheumatic diseases. Arthritis Res Ther 11(3):224

  77. 77.

    Goldring MB, Otero M, Tsuchimochi K, Ijiri K, Li Y (2008) Defining the roles of inflammatory and anabolic cytokines in cartilage metabolism. Ann Rheum Dis 67(Suppl 3):iii75–iii82

  78. 78.

    Goldring SR, Goldring MB (2010) Bone and cartilage in osteoarthritis: is what’s best for one good or bad for the other? Arthritis Res Ther 12(5):143

  79. 79.

    Griffin TM, Guilak F (2005) The role of mechanical loading in the onset and progression of osteoarthritis. Exerc Sport Sci Rev 33(4):195–200

  80. 80.

    Guermazi A, Roemer FW, Hayashi D, Crema MD, Niu J, Zhang Y, Marra MD, Katur A, Lynch JA, El-Khoury GY, Baker K, Hughes LB, Nevitt MC, Felson DT (2011) Assessment of synovitis with contrast-enhanced MRI using a whole-joint semiquantitative scoring system in people with, or at high risk of, knee osteoarthritis: the MOST study. Ann Rheum Dis 70(5):805–811

  81. 81.

    Han SB, Shetty GM, Lee DH, Chae DJ, Seo SS, Wang KH, Yoo SH, Nha KW (2010) Unfavorable results of partial meniscectomy for complete posterior medial meniscus root tear with early osteoarthritis: a 5- to 8-year follow-up study. Arthroscopy 26(10):1326–1332

  82. 82.

    Hashimoto S, Ochs RL, Komiya S, Lotz M (1998) Linkage of chondrocyte apoptosis and cartilage degradation in human osteoarthritis. Arthritis Rheum 41(9):1632–1638

  83. 83.

    Hayashi D, Roemer FW, Katur A, Felson DT, Yang SO, Alomran F, Guermazi A (2011) Imaging of Synovitis in Osteoarthritis: current status and outlook. Semin Arthritis Rheum [Epub ahead of print]

  84. 84.

    Heinegard D, Saxne T (2011) The role of the cartilage matrix in osteoarthritis. Nat Rev Rheumatol 7(1):50–56

  85. 85.

    Hellio Le Graverand MP, Vignon E, Otterness IG, Hart DA (2001) Early changes in lapine menisci during osteoarthritis development: part II: molecular alterations. Osteoarthritis Cartilage 9(1):65–72

  86. 86.

    Higgs R (2011) Osteoarthritis: concentrated efforts to detect early OA. Nat Rev Rheumatol 6(11):616

  87. 87.

    Hirsch R, Lethbridge-Cejku M, Hanson R, Scott WW Jr, Reichle R, Plato CC, Tobin JD, Hochberg MC (1998) Familial aggregation of osteoarthritis: data from the Baltimore Longitudinal Study on Aging. Arthritis Rheum 41(7):1227–1232

  88. 88.

    Hofmann S, Lobenhoffer P, Staubli A, Van Heerwaarden R (2009) Osteotomies of the knee joint in patients with monocompartmental arthritis. Orthopade 38(8):755–769

  89. 89.

    Hunter DJ, Zhang YQ, Niu JB, Tu X, Amin S, Clancy M, Guermazi A, Grigorian M, Gale D, Felson DT (2006) The association of meniscal pathologic changes with cartilage loss in symptomatic knee osteoarthritis. Arthritis Rheum 54(3):795–801

  90. 90.

    Hutton CW, Higgs ER, Jackson PC, Watt I, Dieppe PA (1986) 99mTc HMDP bone scanning in generalised nodal osteoarthritis. I. Comparison of the standard radiograph and four hour bone scan image of the hand. Ann Rheum Dis 45(8):617–621

  91. 91.

    Hutton CW, Higgs ER, Jackson PC, Watt I, Dieppe PA (1986) 99mTc HMDP bone scanning in generalised nodal osteoarthritis. II. The four hour bone scan image predicts radiographic change. Ann Rheum Dis 45(8):622–626

  92. 92.

    Jones MD, Tran CW, Li G, Maksymowych WP, Zernicke RF, Doschak MR (2010) In vivo microfocal computed tomography and micro-magnetic resonance imaging evaluation of antiresorptive and antiinflammatory drugs as preventive treatments of osteoarthritis in the rat. Arthritis Rheum 62(9):2726–2735

  93. 93.

    Kamekura S, Hoshi K, Shimoaka T, Chung U, Chikuda H, Yamada T, Uchida M, Ogata N, Seichi A, Nakamura K, Kawaguchi H (2005) Osteoarthritis development in novel experimental mouse models induced by knee joint instability. Osteoarthritis Cartilage 13(7):632–641

  94. 94.

    Kapoor M, Martel-Pelletier J, Lajeunesse D, Pelletier JP, Fahmi H (2010) Role of proinflammatory cytokines in the pathophysiology of osteoarthritis. Nat Rev Rheumatol 7(1):33–42

  95. 95.

    Karouzakis E, Neidhart M, Gay RE, Gay S (2006) Molecular and cellular basis of rheumatoid joint destruction. Immunol Lett 106(1):8–13

  96. 96.

    Kerkhof HJ, Doherty M, Arden NK, Abramson SB, Attur M, Bos SD, Cooper C, Dennison EM, Doherty SA, Evangelou E, Hart DJ, Hofman A, Javaid K, Kerna I, Kisand K, Kloppenburg M, Krasnokutsky S, Maciewicz RA, Meulenbelt I, Muir KR, Rivadeneira F, Samuels J, Sezgin M, Slagboom E, Smith AJ, Spector TD, Tamm A, Uitterlinden AG, Wheeler M, Zhai G, Zhang W, van Meurs JB, Valdes AM (2011) Large-scale meta-analysis of interleukin-1 beta and interleukin-1 receptor antagonist polymorphisms on risk of radiographic hip and knee osteoarthritis and severity of knee osteoarthritis. Osteoarthritis Cartilage 19(3):265–271

  97. 97.

    Klein-Wieringa IR, Kloppenburg M, Bastiaansen-Jenniskens YM, Yusuf E, Kwekkeboom JC, El-Bannoudi H, Nelissen RG, Zuurmond A, Stojanovic-Susulic V, Van Osch GJ, Toes RE, Ioan-Facsinay A (2011) The infrapatellar fat pad of patients with osteoarthritis has an inflammatory phenotype. Ann Rheum Dis 70(5):851–857

  98. 98.

    Kohn D (1994) Meniscus replacement. Orthopade 23(2):164–170

  99. 99.

    Kohn D, Moreno B (1995) Meniscus insertion anatomy as a basis for meniscus replacement: a morphological cadaveric study. Arthroscopy 11(1):96–103

  100. 100.

    Krasnokutsky S, Belitskaya-Levy I, Bencardino J, Samuels J, Attur M, Regatte R, Rosenthal P, Greenberg J, Schweitzer M, Abramson SB, Rybak L (2011) Quantitative MRI evidence of synovial proliferation is associated with radiographic severity of knee osteoarthritis. Arthritis Rheum. doi:10.1002/art.30471

  101. 101.

    Lajeunesse D (2004) The role of bone in the treatment of osteoarthritis. Osteoarthr Cartil 12(Suppl A):S34–S38

  102. 102.

    Lajeunesse D, Reboul P (2003) Subchondral bone in osteoarthritis: a biologic link with articular cartilage leading to abnormal remodeling. Curr Opin Rheumatol 15(5):628–633

  103. 103.

    Lanyon P, Muir K, Doherty S, Doherty M (2000) Assessment of a genetic contribution to osteoarthritis of the hip: sibling study. BMJ 321(7270):1179–1183

  104. 104.

    Lementowski PW, Zelicof SB (2008) Obesity and osteoarthritis. Am J Orthop (Belle Mead NJ) 37(3):148–151

  105. 105.

    Li B, Aspden RM (1997) Mechanical and material properties of the subchondral bone plate from the femoral head of patients with osteoarthritis or osteoporosis. Ann Rheum Dis 56(4):247–254

  106. 106.

    Li S, Micheletti R (2011) Role of diet in rheumatic disease. Rheum Dis Clin North Am 37(1):119–133

  107. 107.

    Lim AY, Doherty M (2011) What of guidelines for osteoarthritis? Int J Rheum Dis 14(2):136–144

  108. 108.

    Lindberg H (1986) Prevalence of primary coxarthrosis in siblings of patients with primary coxarthrosis. Clin Orthop Relat Res 203:273–275

  109. 109.

    Little CB, Smith MM, Cake MA, Read RA, Murphy MJ, Barry FP (2010) The OARSI histopathology initiative—recommendations for histological assessments of osteoarthritis in sheep and goats. Osteoarthr Cartil 18(Suppl 3):S80–S92

  110. 110.

    Lohmander LS, Englund PM, Dahl LL, Roos EM (2007) The long-term consequence of anterior cruciate ligament and meniscus injuries: osteoarthritis. Am J Sports Med 35(10):1756–1769

  111. 111.

    Lories RJ, Luyten FP (2011) The bone-cartilage unit in osteoarthritis. Nat Rev Rheumatol 7(1):43–49

  112. 112.

    Lories RJ, Peeters J, Bakker A, Tylzanowski P, Derese I, Schrooten J, Thomas JT, Luyten FP (2007) Articular cartilage and biomechanical properties of the long bones in Frzb-knockout mice. Arthritis Rheum 56(12):4095–4103

  113. 113.

    Lories RJ, Peeters J, Szlufcik K, Hespel P, Luyten FP (2009) Deletion of frizzled-related protein reduces voluntary running exercise performance in mice. Osteoarthritis Cartilage 17(3):390–396

  114. 114.

    Loughlin J (2011) Genetic indicators and susceptibility to osteoarthritis. Br J Sports Med 45(4):278–282

  115. 115.

    Loughlin J (2011) Osteoarthritis year 2010 in review: genetics. Osteoarthritis Cartilage 19(4):342–345

  116. 116.

    Lyons TJ, McClure SF, Stoddart RW, McClure J (2006) The normal human chondro-osseous junctional region: evidence for contact of uncalcified cartilage with subchondral bone and marrow spaces. BMC Musculoskelet Disord 7:52

  117. 117.

    Madry H (2010) The subchondral bone: a new frontier in articular cartilage repair. Knee Surg Sports Traumatol Arthrosc 18(4):417–418

  118. 118.

    Madry H, van Dijk CN, Mueller-Gerbl M (2010) The basic science of the subchondral bone. Knee Surg Sports Traumatol Arthrosc 18(4):419–433

  119. 119.

    Mankin HJ, Dorfman H, Lippiello L, Zarins A (1971) Biochemical and metabolic abnormalities in articular cartilage from osteo-arthritic human hips. II. Correlation of morphology with biochemical and metabolic data. J Bone Joint Surg Am 53(3):523–537

  120. 120.

    March L, Amatya B, Osborne RH, Brand C (2010) Developing a minimum standard of care for treating people with osteoarthritis of the hip and knee. Best Pract Res Clin Rheumatol 24(1):121–145

  121. 121.

    Marcu KB, Otero M, Olivotto E, Borzi RM, Goldring MB (2010) NF-kappaB signaling: multiple angles to target OA. Curr Drug Targets 11(5):599–613

  122. 122.

    Mastbergen SC, Lafeber FP (2011) Changes in subchondral bone early in the development of osteoarthritis. Arthritis Rheum 63(9):2561–2563

  123. 123.

    Matsumoto T, Cooper GM, Gharaibeh B, Meszaros LB, Li G, Usas A, Fu FH, Huard J (2009) Cartilage repair in a rat model of osteoarthritis through intraarticular transplantation of muscle-derived stem cells expressing bone morphogenetic protein 4 and soluble Flt-1. Arthritis Rheum 60(5):1390–1405

  124. 124.

    McGonagle D, Tan AL, Carey J, Benjamin M (2010) The anatomical basis for a novel classification of osteoarthritis and allied disorders. J Anat 216(3):279–291

  125. 125.

    Melchiorri C, Meliconi R, Frizziero L, Silvestri T, Pulsatelli L, Mazzetti I, Borzi RM, Uguccioni M, Facchini A (1998) Enhanced and coordinated in vivo expression of inflammatory cytokines and nitric oxide synthase by chondrocytes from patients with osteoarthritis. Arthritis Rheum 41(12):2165–2174

  126. 126.

    Merz D, Liu R, Johnson K, Terkeltaub R (2003) IL-8/CXCL8 and growth-related oncogene alpha/CXCL1 induce chondrocyte hypertrophic differentiation. J Immunol 171(8):4406–4415

  127. 127.

    Messent EA, Ward RJ, Tonkin CJ, Buckland-Wright C (2005) Cancellous bone differences between knees with early, definite and advanced joint space loss; a comparative quantitative macroradiographic study. Osteoarthritis Cartilage 13(1):39–47

  128. 128.

    Mistry D, Oue Y, Chambers MG, Kayser MV, Mason RM (2004) Chondrocyte death during murine osteoarthritis. Osteoarthritis Cartilage 12(2):131–141

  129. 129.

    Miyazaki T, Wada M, Kawahara H, Sato M, Baba H, Shimada S (2002) Dynamic load at baseline can predict radiographic disease progression in medial compartment knee osteoarthritis. Ann Rheum Dis 61(7):617–622

  130. 130.

    Mollenhauer JA (2011) Closing ranks: the chondrocytes’ move in bad times or biomechanical job sharing? Arthritis Rheum 63(6):1475–1476

  131. 131.

    Moore EE, Bendele AM, Thompson DL, Littau A, Waggie KS, Reardon B, Ellsworth JL (2005) Fibroblast growth factor-18 stimulates chondrogenesis and cartilage repair in a rat model of injury-induced osteoarthritis. Osteoarthritis Cartilage 13(7):623–631

  132. 132.

    Mow VC, Kuei SC, Lai WM, Armstrong CG (1980) Biphasic creep and stress relaxation of articular cartilage in compression? Theory and experiments. J Biomech Eng 102(1):73–84

  133. 133.

    Murphy G, Nagase H (2008) Reappraising metalloproteinases in rheumatoid arthritis and osteoarthritis: destruction or repair? Nat Clin Pract Rheumatol 4(3):128–135

  134. 134.

    Muthuri SG, McWilliams DF, Doherty M, Zhang W (2011) History of knee injuries and knee osteoarthritis: a meta-analysis of observational studies. Osteoarthr Cartil [Epub ahead of print]

  135. 135.

    Myers SL, Flusser D, Brandt KD, Heck DA (1992) Prevalence of cartilage shards in synovium and their association with synovitis in patients with early and endstage osteoarthritis. J Rheumatol 19(8):1247–1251

  136. 136.

    Neame RL, Muir K, Doherty S, Doherty M (2004) Genetic risk of knee osteoarthritis: a sibling study. Ann Rheum Dis 63(9):1022–1027

  137. 137.

    Neogi T, Felson D, Niu J, Lynch J, Nevitt M, Guermazi A, Roemer F, Lewis CE, Wallace B, Zhang Y (2009) Cartilage loss occurs in the same subregions as subchondral bone attrition: a within-knee subregion-matched approach from the Multicenter Osteoarthritis Study. Arthritis Rheum 61(11):1539–1544

  138. 138.

    Neogi T, Nevitt M, Niu J, Sharma L, Roemer F, Guermazi A, Lewis CE, Torner J, Javaid K, Felson D (2010) Subchondral bone attrition may be a reflection of compartment-specific mechanical load: the MOST Study. Ann Rheum Dis 69(5):841–844

  139. 139.

    Neogi T, Zhang Y (2011) Osteoarthritis prevention. Curr Opin Rheumatol 23(2):185–191

  140. 140.

    Niemeyer P, Schmal H, Hauschild O, von Heyden J, Sudkamp NP, Kostler W (2010) Open-wedge osteotomy using an internal plate fixator in patients with medial-compartment gonarthritis and varus malalignment: 3-year results with regard to preoperative arthroscopic and radiographic findings. Arthroscopy 26(12):1607–1616

  141. 141.

    Noble J, Hamblen DL (1975) The pathology of the degenerate meniscus lesion. J Bone Joint Surg Br 57(2):180–186

  142. 142.

    Noble J, Turner PG (1986) The function, pathology, and surgery of the meniscus. Clin Orthop Relat Res 210:62–68

  143. 143.

    Oakley SP, Portek I, Szomor Z, Appleyard RC, Ghosh P, Kirkham BW, Murrell GA, Lassere MN (2005) Arthroscopy–a potential “gold standard” for the diagnosis of the chondropathy of early osteoarthritis. Osteoarthritis Cartilage 13(5):368–378

  144. 144.

    Oegema T, Visco D (1999) Animal models of osteoarthritis. Animal models in orthopaedic research. CRC Press, Boca Raton

  145. 145.

    Oehler S, Neureiter D, Meyer-Scholten C, Aigner T (2002) Subtyping of osteoarthritic synoviopathy. Clin Exp Rheumatol 20(5):633–640

  146. 146.

    Offit K (2011) Personalized medicine: new genomics, old lessons. Hum Genet 130(1):3–14

  147. 147.

    Olivotto E, Vitellozzi R, Fernandez P, Falcieri E, Battistelli M, Burattini S, Facchini A, Flamigni F, Santi S, Borzi RM (2007) Chondrocyte hypertrophy and apoptosis induced by GROalpha require three-dimensional interaction with the extracellular matrix and a co-receptor role of chondroitin sulfate and are associated with the mitochondrial splicing variant of cathepsin B. J Cell Physiol 210(2):417–427

  148. 148.

    Orita S, Koshi T, Mitsuka T, Miyagi M, Inoue G, Arai G, Ishikawa T, Hanaoka E, Yamashita K, Yamashita M, Eguchi Y, Toyone T, Takahashi K, Ohtori S (2011) Associations between proinflammatory cytokines in the synovial fluid and radiographic grading and pain-related scores in 47 consecutive patients with osteoarthritis of the knee. BMC Musculoskelet Disord 12:144

  149. 149.

    Patra D, Sandell LJ (2011) Recent advances in biomarkers in osteoarthritis. Curr Opin Rheumatol 23(5):465–470

  150. 150.

    Pauli C, Grogan SP, Patil S, Otsuki S, Hasegawa A, Koziol J, Lotz MK, D’Lima DD (2011) Macroscopic and histopathologic analysis of human knee menisci in aging and osteoarthritis. Osteoarthr Cartil. doi:10.1016/j.joca.2011.05.008

  151. 151.

    Penzo M, Massa PE, Olivotto E, Bianchi F, Borzi RM, Hanidu A, Li X, Li J, Marcu KB (2009) Sustained NF-kappaB activation produces a short-term cell proliferation block in conjunction with repressing effectors of cell cycle progression controlled by E2F or FoxM1. J Cell Physiol 218(1):215–227

  152. 152.

    Poole R, Blake S, Buschmann M, Goldring S, Laverty S, Lockwood S, Matyas J, McDougall J, Pritzker K, Rudolphi K, van den Berg W, Yaksh T (2010) Recommendations for the use of preclinical models in the study and treatment of osteoarthritis. Osteoarthr Cartil 18(Suppl 3):S10–S16

  153. 153.

    Pritzker KP, Gay S, Jimenez SA, Ostergaard K, Pelletier JP, Revell PA, Salter D, van den Berg WB (2006) Osteoarthritis cartilage histopathology: grading and staging. Osteoarthritis Cartilage 14(1):13–29

  154. 154.

    Radin EL, Paul IL, Rose RM (1972) Role of mechanical factors in pathogenesis of primary osteoarthritis. Lancet (7749):519–522

  155. 155.

    Radin EL, Paul IL, Tolkoff MJ (1970) Subchondral bone changes in patients with early degenerative joint disease. Arthritis Rheum 13(4):400–405

  156. 156.

    Radin EL, Rose RM (1986) Role of subchondral bone in the initiation and progression of cartilage damage. Clin Orthop Relat Res (213):34–40

  157. 157.

    Riyami M, Rolf C (2009) Evaluation of microfracture of traumatic chondral injuries to the knee in professional football and rugby players. J Orthop Surg Res 4:13

  158. 158.

    Rolauffs B, Rothdiener M, Bahrs C, Badke A, Weise K, Kuettner KE, Kurz B, Aurich M, Grodzinsky AJ, Aicher WK (2011) Onset of preclinical osteoarthritis: the angular spatial organization permits early diagnosis. Arthritis Rheum 63(6):1637–1647

  159. 159.

    Roos EM, Herzog W, Block JA, Bennell KL (2011) Muscle weakness, afferent sensory dysfunction and exercise in knee osteoarthritis. Nat Rev Rheumatol 7(1):57–63

  160. 160.

    Roos H, Adalberth T, Dahlberg L, Lohmander LS (1995) Osteoarthritis of the knee after injury to the anterior cruciate ligament or meniscus: the influence of time and age. Osteoarthritis Cartilage 3(4):261–267

  161. 161.

    Rupp S, Seil R, Kohn D (2002) Meniscus lesions. Orthopade 31(8):812–828

  162. 162.

    Sagar DR, Staniaszek LE, Okine BN, Woodhams S, Norris LM, Pearson RG, Garle MJ, Alexander SP, Bennett AJ, Barrett DA, Kendall DA, Scammell BE, Chapman V (2010) Tonic modulation of spinal hyperexcitability by the endocannabinoid receptor system in a rat model of osteoarthritis pain. Arthritis Rheum 62(12):3666–3676

  163. 163.

    Saito T, Fukai A, Mabuchi A, Ikeda T, Yano F, Ohba S, Nishida N, Akune T, Yoshimura N, Nakagawa T, Nakamura K, Tokunaga K, Chung UI, Kawaguchi H (2010) Transcriptional regulation of endochondral ossification by HIF-2alpha during skeletal growth and osteoarthritis development. Nat Med 16(6):678–686

  164. 164.

    Sambrook PN, MacGregor AJ, Spector TD (1999) Genetic influences on cervical and lumbar disc degeneration: a magnetic resonance imaging study in twins. Arthritis Rheum 42(2):366–372

  165. 165.

    Schaffler MB, Radin EL, Burr DB (1989) Mechanical and morphological effects of strain rate on fatigue of compact bone. Bone 10(3):207–214

  166. 166.

    Segal NA, Torner JC, Felson D, Niu J, Sharma L, Lewis CE, Nevitt M (2009) Effect of thigh strength on incident radiographic and symptomatic knee osteoarthritis in a longitudinal cohort. Arthritis Rheum 61(9):1210–1217

  167. 167.

    Sellam J, Berenbaum F (2010) The role of synovitis in pathophysiology and clinical symptoms of osteoarthritis. Nat Rev Rheumatol 6(11):625–635

  168. 168.

    Shane Anderson A, Loeser RF (2010) Why is osteoarthritis an age-related disease? Best Pract Res Clin Rheumatol 24(1):15–26

  169. 169.

    Sharma L, Kapoor D, Issa S (2006) Epidemiology of osteoarthritis: an update. Curr Opin Rheumatol 18(2):147–156

  170. 170.

    Sharma L, Song J, Felson DT, Cahue S, Shamiyeh E, Dunlop DD (2001) The role of knee alignment in disease progression and functional decline in knee osteoarthritis. JAMA 286(2):188–195

  171. 171.

    Slemenda C, Heilman DK, Brandt KD, Katz BP, Mazzuca SA, Braunstein EM, Byrd D (1998) Reduced quadriceps strength relative to body weight: a risk factor for knee osteoarthritis in women? Arthritis Rheum 41(11):1951–1959

  172. 172.

    Sokoloff L (1993) Microcracks in the calcified layer of articular cartilage. Arch Pathol Lab Med 117(2):191–195

  173. 173.

    Sommerlath K (1989) The importance of the meniscus in unstable knees. A comparative study. Am J Sports Med 17(6):773–777

  174. 174.

    Stecher RM (1941) Heberden’s nodes: heredity in hypertrophic arthritis of the finger joints. Am J Med Sci 201:801–809

  175. 175.

    Strassle BW, Mark L, Leventhal L, Piesla MJ, Jian Li X, Kennedy JD, Glasson SS, Whiteside GT (2010) Inhibition of osteoclasts prevents cartilage loss and pain in a rat model of degenerative joint disease. Osteoarthritis Cartilage 18(10):1319–1328

  176. 176.

    Taljanovic MS, Graham AR, Benjamin JB, Gmitro AF, Krupinski EA, Schwartz SA, Hunter TB, Resnick DL (2008) Bone marrow edema pattern in advanced hip osteoarthritis: quantitative assessment with magnetic resonance imaging and correlation with clinical examination, radiographic findings, and histopathology. Skeletal Radiol 37(5):423–431

  177. 177.

    Tanamas S, Hanna FS, Cicuttini FM, Wluka AE, Berry P, Urquhart DM (2009) Does knee malalignment increase the risk of development and progression of knee osteoarthritis? A systematic review. Arthritis Rheum 61(4):459–467

  178. 178.

    Thambyah A, Broom N (2009) On new bone formation in the pre-osteoarthritic joint. Osteoarthritis Cartilage 17(4):456–463

  179. 179.

    Valdes AM, Doherty M, Spector TD (2008) The additive effect of individual genes in predicting risk of knee osteoarthritis. Ann Rheum Dis 67(1):124–127

  180. 180.

    Valdes AM, Spector TD (2009) The contribution of genes to osteoarthritis. Med Clin North Am 93(1):45–66

  181. 181.

    Valdes AM, Spector TD (2010) The clinical relevance of genetic susceptibility to osteoarthritis. Best Pract Res Clin Rheumatol 24(1):3–14

  182. 182.

    Valdes AM, Spector TD (2010) Genetic epidemiology of hip and knee osteoarthritis. Nat Rev Rheumatol 7(1):23–32

  183. 183.

    Valdes AM, Spector TD (2010) The genetic epidemiology of osteoarthritis. Curr Opin Rheumatol 22(2):139–143

  184. 184.

    Valdes AM, Spector TD (2011) Genetic epidemiology of hip and knee osteoarthritis. Nat Rev Rheumatol 7(1):23–32

  185. 185.

    van den Berg WB (2011) Osteoarthritis year 2010 in review: pathomechanisms. Osteoarthritis Cartilage 19(4):338–341

  186. 186.

    van der Kraan PM, van den Berg WB (2008) Osteoarthritis in the context of ageing and evolution. Loss of chondrocyte differentiation block during ageing. Ageing Res Rev 7(2):106–113

  187. 187.

    van Meurs JB, Uitterlinden AG, Stolk L, Kerkhof HJ, Hofman A, Pols HA, Bierma-Zeinstra SM (2009) A functional polymorphism in the catechol-O-methyltransferase gene is associated with osteoarthritis-related pain. Arthritis Rheum 60(2):628–629

  188. 188.

    Vanden Berg-Foels WS, Schwager SJ, Todhunter RJ, Reeves AP (2011) Femoral head shape differences during development may identify hips at risk of degeneration. Ann Biomed Eng. doi:10.1007/s10439-011-0393-3

  189. 189.

    Vener MJ, Thompson RC Jr, Lewis JL, Oegema TR Jr (1992) Subchondral damage after acute transarticular loading: an in vitro model of joint injury. J Orthop Res 10(6):759–765

  190. 190.

    Venkatesan N, Barre L, Magdalou J, Mainard D, Netter P, Fournel-Gigleux S, Ouzzine M (2009) Modulation of xylosyltransferase I expression provides a mechanism regulating glycosaminoglycan chain synthesis during cartilage destruction and repair. FASEB J 23(3):813–822

  191. 191.

    Verma P, Dalal K (2011) ADAMTS-4 and ADAMTS-5: key enzymes in osteoarthritis. J Cell Biochem. doi:10.1002/jcb.23298

  192. 192.

    Vignon E, Arlot M, Hartmann D, Moyen B, Ville G (1983) Hypertrophic repair of articular cartilage in experimental osteoarthrosis. Ann Rheum Dis 42(1):82–88

  193. 193.

    Vignon E, Bejui J, Mathieu P, Hartmann JD, Ville G, Evreux JC, Descotes J (1987) Histological cartilage changes in a rabbit model of osteoarthritis. J Rheumatol 14(Spec No):104–106

  194. 194.

    Vincenti MP, Brinckerhoff CE (2002) Transcriptional regulation of collagenase (MMP-1, MMP-13) genes in arthritis: integration of complex signaling pathways for the recruitment of gene-specific transcription factors. Arthritis Res 4(3):157–164

  195. 195.

    Vogel WF, Abdulhussein R, Ford CE (2006) Sensing extracellular matrix: an update on discoidin domain receptor function. Cell Signal 18(8):1108–1116

  196. 196.

    von der Mark K, Kirsch T, Nerlich A, Kuss A, Weseloh G, Gluckert K, Stoss H (1992) Type X collagen synthesis in human osteoarthritic cartilage. Indication of chondrocyte hypertrophy. Arthritis Rheum 35(7):806–811

  197. 197.

    Wang SX, Laverty S, Dumitriu M, Plaas A, Grynpas MD (2007) The effects of glucosamine hydrochloride on subchondral bone changes in an animal model of osteoarthritis. Arthritis Rheum 56(5):1537–1548

  198. 198.

    Wang Y, Dempsey AR, Lloyd DG, Mills PM, Wrigley T, Bennell KL, Metcalf B, Hanna F, Cicuttini FM (2011) Patellofemoral and tibiofemoral articular cartilage and subchondral bone health following arthroscopic partial medial meniscectomy. Knee Surg Sports Traumatol Arthrosc. doi:10.1007/s00167-011-1681-z

  199. 199.

    Wieland HA, Michaelis M, Kirschbaum BJ, Rudolphi KA (2005) Osteoarthritis—an untreatable disease? Nat Rev Drug Discov 4(4):331–344

  200. 200.

    Xu L, Servais J, Polur I, Kim D, Lee PL, Chung K, Li Y (2010) Attenuation of osteoarthritis progression by reduction of discoidin domain receptor 2 in mice. Arthritis Rheum 62(9):2736–2744

  201. 201.

    Zhang Y, Jordan JM (2008) Epidemiology of osteoarthritis. Rheum Dis Clin North Am 34(3):515–529

  202. 202.

    Zhang Y, Jordan JM (2010) Epidemiology of osteoarthritis. Clin Geriatr Med 26(3):355–369

Download references

Acknowledgments

Henning Madry received funding for OA research from the German Osteoarthritis Foundation (Deutsche Arthrose-Hilfe). Frank Luyten is supported and received some funding for OA research from the seventh framework program TREAT-OA network (www.treatoa.eu). Andrea Facchini received funding from the Regione Emilia Romagna, Italy (PRRU 2007-2009 “Regenerative medicine in osteo-articular diseases”), Fondazione Monte dei Paschi di Siena, Fondazione CARISBO, Italy, FIRB and MIUR, Italy.

Author information

Correspondence to Henning Madry.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Madry, H., Luyten, F.P. & Facchini, A. Biological aspects of early osteoarthritis. Knee Surg Sports Traumatol Arthrosc 20, 407–422 (2012). https://doi.org/10.1007/s00167-011-1705-8

Download citation

Keywords

  • Articular chondrocytes
  • Articular cartilage
  • Early OA