Abstract
The cellular and molecular mechanisms responsible for the initiation and progression of osteoarthritis (OA), and in particular cartilage degeneration in OA, are not completely understood. Increasing evidence implicates developmental processes in OA etiology and pathogenesis. Herein, we review this evidence. We first examine subtle changes in cartilage development and the specification and formation of joints, which predispose to OA development, and second, we review the switch from an articular to a hypertrophic chondrocyte phenotype that is thought to be part of the OA pathological process ultimately resulting in cartilage degeneration. The latest studies are summarized and we discuss the concepts emerging from these findings in cartilage biology, in the light of our understanding of the developmental processes involved.
Key Points
-
Links between skeletal development and osteoarthritis (OA) have been identified
-
Disturbances in joint and cartilage development can predispose to OA, and mechanisms by which they can be controlled will inform novel repair approaches
-
Joint cavitation events are linked to OA
-
Ectopic initiation of chondrocyte hypertrophy contributes to OA pathogenesis
-
Runx2 and hypoxia-inducible factor 2α are key transcription factors promoting chondrocyte hypertrophy during development and OA
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Change history
01 February 2013
In the version of this article initially published, the authors omitted to cite the original research papers by Zhang, Y. et al. and Zhang, Q. et al. showing that doublecortin is expressed by articular chondrocytes (Biophys. Res. Commun. 363, 694–700 [2007]; Genesis 49, 75–82 [2011]). These two papers have now been included in the HTML and PDF versions of the review.
References
Thorogood, P. V. & Hinchliffe, J. R. An analysis of the condensation process during chondrogenesis in the embryonic chick hind limb. J. Embryol. Exp. Morphol. 33, 581–606 (1975).
Toole, B. P. Hyaluronate inhibition of chondrogenesis: antagonism of thyroxine, growth hormone, and calcitonin. Science 180, 302–303 (1973).
Onyekwelu, I. Goldring, M. B. & Hidaka, C. Chondrogenesis, joint formation, and articular cartilage regeneration. J. Cell Biochem. 107, 383–392 (2009).
Eshkar-Oren, I. et al. The forming limb skeleton serves as a signaling center for limb vasculature patterning via regulation of Vegf. Development 136, 1263–1272 (2009).
Mundlos, S. & Olsen, B. R. Heritable diseases of the skeleton. Part II: Molecular insights into skeletal development-matrix components and their homeostasis. FASEB J. 11, 227–233 (1997).
Li, Y., Toole, B. P., Dealy, C. N. & Kosher, R. A. Hyaluronan in limb morphogenesis. Dev. Biol. 305, 411–420 (2007).
Sandell, L. J., Nalin, A. M. & Reife, R. A. Alternative splice form of type II procollagen mRNA (IIA) is predominant in skeletal precursors and non-cartilaginous tissues during early mouse development. Dev. Dyn. 199, 129–140 (1994).
Matsumoto, K. et al. Conditional inactivation of Has2 reveals a crucial role for hyaluronan in skeletal growth, patterning, chondrocyte maturation and joint formation in the developing limb. Development 136, 2825–2835 (2009).
Woods, A., Wang, G. & Beier, F. Regulation of chondrocyte differentiation by the actin cytoskeleton and adhesive interactions. J. Cell Physiol. 213, 1–8 (2007).
Xu, L. et al. Attenuation of osteoarthritis progression by reduction of discoidin domain receptor 2 in mice. Arthritis Rheum. 62, 2736–2744 (2010).
Aigner, T. et al. Reexpression of type IIA procollagen by adult articular chondrocytes in osteoarthritic cartilage. Arthritis Rheum. 42, 1443–1450 (1999).
Sandy, J. D., Barrach, H. J., Flanner, C. R. & Plaas, A. H. The biosynthetic response of the mature chondrocyte in early osteoarthritis. J. Rheumatol. 14, 16–19 (1987).
Roughley, P. J. & White, R. J. Age-related changes in the structure of the proteoglycan subunits from human articular cartilage. J. Biol. Chem. 255, 217–224 (1980).
Bayliss, M. T., Osborne, D., Woodhouse, S. & Davidson, S. Sulfation of chondroitin sulfate in human articular cartilage. The effect of age, topographical position, and zone of cartilage on tissue composition. J. Biol. Chem. 274, 15892–15900 (1999).
Hickery, M. S. et al. Age-related changes in the response of human articular cartilage to IL-1α and transforming growth factor-β (TGF-β): chondrocytes exhibit a diminished sensitivity to TGF-β. J. Biol. Chem. 278, 53063–53071 (2003).
Ginsburg, V., Weissbach, A. & Maxwell, E. S. Formation of glucuronic acid from uridinediphosphate glucuronic acid. Biochim. Biophys. Acta 28, 649–650 (1958).
Vigetti, D. et al. Molecular cloning and characterization of UDP-glucose dehydrogenase from the amphibian Xenopus laevis and its involvement in hyaluronan synthesis. J. Biol. Chem. 281, 8254–8263 (2006).
Clarkin, C. E. et al. Regulation of UDP-glucose dehydrogenase is sufficient to modulate hyaluronan production and release, control sulfated GAG synthesis, and promote chondrogenesis. J. Cell. Physiol. 226, 749–761 (2011).
Bursell, L. et al. Src kinase inhibition promotes the chondrocyte phenotype. Arthritis Res. Ther. 9, R105 (2007).
Woods, A., Khan, S. & Beier, F. C-type natriuretic peptide regulates cellular condensation and glycosaminoglycan synthesis during chondrogenesis. Endocrinology, 148, 5030–5041 (2007).
Kornak, U. & Mundlos, S. Genetic disorders of the skeleton: a developmental approach. Am. J. Hum. Genet., 73, 447–474 (2003).
Bi, W., Deng, J. M., Zhang, Z., Behringer, R. R. & de Crombrugghe, B. Sox9 is required for cartilage formation. Nat. Genet. 22, 85–89 (1999).
Akiyama, H. et al. Osteo-chondroprogenitor cells are derived from Sox9 expressing precursors. Proc. Natl Acad. Sci. USA 102, 14665–14670 (2005).
Hardingham, T. E., Oldershaw, R. A. & Tew, S. R. Cartilage, SOX9 and Notch signals in chondrogenesis. J. Anat. 209, 469–480 (2006).
Pitsillides, A. A. & Ashhurst, D. E. A critical evaluation of specific aspects of joint development. Dev. Dyn. 237, 2284–2294 (2008).
Mead, T. J. & Yutzey, K. E. Notch pathway regulation of chondrocyte differentiation and proliferation during appendicular and axial skeleton development. Proc. Natl Acad. Sci. USA 106, 14420–14425 (2009).
Li, K. & Thorne, C. Adult presentation of Stickler syndrome type III. Clin. Rheumatol, 29, 795–797 (2010).
Hartmann, C. & Tabin, C. J. Dual roles of Wnt signaling during chondrogenesis in the chicken limb. Development 127, 3141–3159 (2000).
Zhu, M. et al. Activation of β-catenin signaling in articular chondrocytes leads to osteoarthritis-like phenotype in adult β-catenin conditional activation mice. J. Bone Miner. Res., 24, 12–21 (2009).
Zhu, M. et al. Inhibition of β-catenin signaling in articular chondrocytes results in articular cartilage destruction. Arthritis Rheum. 58, 2053–2064 (2008).
Valdes, A. M. et al. Variation at the ANP32A gene is associated with risk of hip osteoarthritis in women. Arthritis Rheum. 60, 2046–2054 (2009).
Dao, D. Y. et al. Axin2 regulates chondrocyte maturation and axial skeletal development. J. Orthop. Res. 28, 89–95 (2010).
Tabin, C. & Wolpert, L. Rethinking the proximodistal axis of the vertebrate limb in the molecular era. Genes Dev. 21, 1433–1442 (2007).
Goff, D. J. & Tabin, C. J. Analysis of Hoxd-13 and Hoxd-11 misexpression in chick limb buds reveals that Hox genes affect both bone condensation and growth. Development 124, 627–636 (1997).
Tickle, C. Making digit patterns in the vertebrate limb. Nat. Rev. Mol. Cell Biol. 7, 45–53 (2006).
Kirn-Safran, C. B., Gomes, R. R., Brown, A. J. & Carson, D. D. Heparan sulfate proteoglycans: coordinators of multiple signaling pathways during chondrogenesis. Birth Defects Res. C Embryo Today 72, 69–88 (2004).
Dhoot, G. K. et al. Regulation of Wnt signaling and embryo patterning by an extracellular sulfatase. Science 293, 1663–1666 (2001).
Otsuki, S. et al. Extracellular sulfatases support cartilage homeostasis by regulating BMP and FGF signaling pathways. Proc. Natl Acad. Sci. USA 107, 10202–10207 (2010).
Archer, C. W. Skeletal development and osteoarthritis. Ann. Rheum. Dis. 53, 624–630 (1994).
Niedermaier, M. et al. An inversion involving the mouse Shh locus results in brachydactyly through dysregulation of Shh expression. J. Clin. Invest. 115, 900–909 (2005).
Stattin, E. L., Tegner, Y., Domellöf, M. & Dahl, N. Familial osteochondritis dissecans associated with early osteoarthritis and disproportionate short stature. Osteoarthritis Cartilage 16, 890–896 (2008).
Miyaki, S. et al. MicroRNA-140 plays dual roles in both cartilage development and homeostasis. Genes Dev. 24, 1173–1185 (2010).
Ferraro, B., Wilder, F. V. & Leaverton, P. E. Site specific osteoarthritis and the index to ring finger length ratio. Osteoarthritis Cartilage 18, 354–357 (2010).
Villavicencio-Lorini, P. et al. Homeobox genes d11–d13 and a13 control mouse autopod cortical bone and joint formation. J. Clin. Invest., 120, 1994–2004 (2010).
Thomas, J. T. et al. A human chondrodysplasia due to a mutation in a TGF-β superfamily member. Nat. Genet. 12, 315–317 (1996).
Storm, E. E. et al. Limb alterations in brachypodism mice due to mutations in a new member of the TGF β-superfamily. Nature 368, 639–643 (1994).
Evangelou, E. et al. Large-scale analysis of association between GDF5 and FRZB variants and osteoarthritis of the hip, knee, and hand. Arthritis Rheum. 60, 1710–1721 (2009).
Valdes, A. M. & Spector, T. D. Genetic epidemiology of hip and knee osteoarthritis. Nat. Rev. Rheumatol. 7, 23–32 (2011).
Chapman, K. et al. A meta-analysis of European and Asian cohorts reveals a global role of a functional SNP in the 5′ UTR of GDF5 with osteoarthritis susceptibility. Hum. Mol. Genet. 17, 1497–1504 (2008).
Evangelou, E. et al. Meta-analysis of genome-wide association studies confirms a susceptibility locus for knee osteoarthritis on chromosome 7q22. Ann. Rheum. Dis. 70, 349–355 (2011).
Wang, K. et al. Association of a single nucleotide polymorphism in Tbx4 with developmental dysplasia of the hip: a case-control study. Osteoarthritis Cartilage 18, 1592–1595 (2010).
Daans, M., Luyten, F. P. & Lories, R. J. GDF5 deficiency in mice is associated with instability-driven joint damage, gait and subchondral bone changes. Ann. Rheum. Dis. 70, 208–213 (2011).
Kavanagh, E. et al. Differential regulation of GDF-5 and FGF-2/4 by immobilisation in ovo exposes distinct roles in joint formation. Dev. Dyn. 235, 826–834 (2006).
Poulet, B., McNeil, J. & Pitsillides, A. A. Is follistatin-like 3 or fstl3 necessary for joint health? Osteoarthritis Cartilage 18 (Suppl. 2), S13–S13 (2010).
Lamb, K. J. et al. Diverse range of fixed positional deformities and bone growth restraint provoked by flaccid paralysis in embryonic chicks. Int. J. Exp. Pathol., 84, 191–199 (2003).
Pitsillides, A. A. Early effects of embryonic movement: 'a shot out of the dark'. J. Anat. 208, 417–431 (2006).
Hyde, G. et al. Lineage tracing using matrilin-1 gene expression reveals that articular chondrocytes exist as the joint interzone forms. Dev. Biol. 304, 825–833 (2007).
Zhang, Y. et al. Doublecortin is expressed in articular chondrocytes. Biochem. Biophys. Res. Commun. 363, 694–700 (2007).
Zhang, Q. et al. Expression of doublecortin reveals articular chondrocyte lineage in mouse embryonic limbs. Genesis 49, 75–82 (2011).
Koyama, E. et al. A distinct cohort of progenitor cells participates in synovial joint and articular cartilage formation during mouse limb skeletogenesis. Dev. Biol. 316, 62–73 (2008).
Spater, D. et al. Role of canonical Wnt-signalling in joint formation. Eur. Cell. Mater. 12, 71–80 (2006).
Church, V. et al. Expression and function of Bapx1 during chick limb development. Anat. Embryol. (Berl.) 209, 461–469 (2005).
Brunet, L. J., McMahon, J. A., McMahaon, M. P. & Harland, R. M. Noggin, cartilage morphogenesis, and joint formation in the mammalian skeleton. Science 280, 1455–1457 (1998).
Lizarraga, G., Lichtler, A., Upholt, W. B. & Kosher, R. A. Studies on the role of Cux1 in regulation of the onset of joint formation in the developing limb. Dev. Biol. 243, 44–54 (2002).
Hartmann, C. & Tabin, C. J. Wnt-14 plays a pivotal role in inducing synovial joint formation in the developing appendicular skeleton. Cell 104, 341–351 (2001).
Dowthwaite, G. P., Edwards, J. C. & Pitsillides, A. A. An essential role for the interaction between hyaluronan and hyaluronan binding proteins during joint development. J. Histochem. Cytochem. 46, 641–651 (1998).
Edwards, J. C. et al. The formation of human synovial joint cavities: a possible role for hyaluronan and CD44 in altered interzone cohesion. J. Anat. 185, 355–367 (1994).
Dell'accio, F., DeBari, C., Eltawil, N. M., Vanhummelen, P. & Pitzalis, C. Identification of the molecular response of articular cartilage to injury, by microarray screening: Wnt-16 expression and signaling after injury and in osteoarthritis. Arthritis Rheum. 58, 1410–1421 (2008).
Blom, A. B. et al. Involvement of the Wnt signaling pathway in experimental and human osteoarthritis: prominent role of Wnt-induced signaling protein 1. Arthritis Rheum. 60, 501–512 (2009).
Lories, R. J. et al. Articular cartilage and biomechanical properties of the long bones in Frzb-knockout mice. Arthritis Rheum. 56, 4095–4103 (2007).
Loughlin, J. et al. Functional variants within the secreted frizzled-related protein 3 gene are associated with hip osteoarthritis in females. Proc. Natl Acad. Sci. USA 101, 9757–9762 (2004).
Lovinescu, I., Koyama, E. & Pacifici, M. Roles of FGF-10 on the development of diathrodial limb joints. Penn. Dent. J. (Phila) 103, 5–9 (2003).
Iwamoto, M. et al. Transcription factor ERG and joint and articular cartilage formation during mouse limb and spine skeletogenesis. Dev. Biol. 305, 40–51 (2007).
Garciadiego-Cazares, D. et al. Coordination of chondrocyte differentiation and joint formation by alpha5beta1 integrin in the developing appendicular skeleton. Development 131, 4735–4742 (2004).
Hill, T. P. et al. Multiple roles of mesenchymal β-catenin during murine limb patterning. Development 133, 1219–1229 (2006).
Snow, H. E. et al. Versic5n expression during skeletal/joint morphogenesis and patterning of muscle and nerve in the embryonic mouse limb. Anat. Rec. A Discov. Mol. Cell Evol. Biol., 282, 95–105 (2005).
Pitsillides, A. A. et al. Alterations in hyaluronan synthesis during developing joint cavitation. J. Histochem. Cytochem. 43, 263–273 (1995).
Capehart, A. A. Proteolytic cleavage of versican during limb joint development. Anat. Rec. (Hoboken) 293, 208–214 (2010).
Edwards, J. C. et al. Matrix metalloproteinases in the formation of human synovial joint cavities. J. Anat. 188, 355–360 (1996).
Bastow, E. R. et al. Selective activation of the MEK–ERK pathway is regulated by mechanical stimuli in forming joints and promotes pericellular matrix formation. J. Biol. Chem. 280, 11749–11758 (2005).
Lamb, K. J. et al. Defining boundaries during joint cavity formation: going out on a limb. Int. J. Exp. Pathol. 84, 55–67 (2003).
Lewthwaite, J. C. et al. A specific mechanomodulatory role for p38 MAPK in embryonic joint articular surface cell MEK–ERK pathway regulation. J. Biol. Chem. 281, 11011–11018 (2006).
Wheeler, B. C., Wheeler-Jones, C. & Pitsillides, A. A. A novel role for the inflammatory mediator, cyclo-oxygenase-2, in regulating hyaluronan-synthesis and binding during normal joint development. Transactions 33, 0373 (2008).
Dowthwaite, G. P. et al. The surface of articular cartilage contains a progenitorcell population. J. Cell Sci. 117, 889–897 (2004).
Williams, R. et al. Identification and clonal characterisation of a progenitor cell sub-population in normal human articular cartilage. PLoS ONE 5 e13246 (2010).
Dy, P. et al. Synovial joint morphogenesis requires the chondrogenic action of Sox5 and Sox6 in growth plate and articular cartilage. Dev. Biol. 341, 346–359 (2010).
Gunnell, L. M. et al. TAK1 regulates cartilage and joint development via the MAPK and BMP signaling pathways. J. Bone Miner. Res. 25, 1784–1797 (2010).
Gao, Y. et al. The zinc finger transcription factors Osr1 and Osr2 control synovial joint formation. Dev. Biol. 352, 83–91 (2011).
Provot, S. & Schipani, E. Fetal growth plate: a developmental model of cellular adaptation to hypoxia. Ann. NY Acad. Sci. 1117, 26–39 (2007).
Kannu, P. et al. Premature arthritis is a distinct type II collagen phenotype. Arthritis Rheum. 62, 1421–1430 (2010).
Baker-LePain, J. C. & Lane, N. E. Relationship between joint shape and the development of osteoarthritis. Curr. Opin. Rheumatol. 22, 538–543 (2010).
Kronenberg, H. M. Developmental regulation of the growth plate. Nature 423, 332–336 (2003).
Ballock, R. T. & O'Keefe, R. J. Physiology and pathophysiology of the growth plate. Birth Defects Res. C Embryo Today 69, 123–143 (2003).
Drissi, H. et al. Transcriptional regulation of chondrocyte maturation: potential involvement of transcription factors in OA pathogenesis. Mol. Aspects Med. 26, 169–179 (2005).
Chung, U. I. Essential role of hypertrophic chondrocytes in endochondral bone development. Endocr. J. 51, 19–24 (2004).
von der Mark, K. et al. Type X collagen synthesis in human osteoarthritic cartilage. Indication of chondrocyte hypertrophy. Arthritis Rheum. 35, 806–811 (1992).
Hoyland, J. A. et al. Distribution of type X collagen mRNA in normal and osteoarthritic human cartilage. Bone Miner. 15, 151–163 (1991).
Tchetina, E. V., Squires, G. & Poole, A. R. Increased type II collagen degradation and very early focal cartilage degeneration is associated with upregulation of chondrocyte differentiation related genes in early human articular cartilage lesions. J. Rheumatol. 32, 876–886 (2005).
Pullig, O. et al. Chondrocyte differentiation in human osteoarthritis: expression of osteocalcin in normal and osteoarthritic cartilage and bone. Calcif. Tissue Int. 67, 230–240 (2000).
Cecil, D. L. et al. The pattern recognition receptor CD36 is a chondrocyte hypertrophy marker associated with suppression of catabolic responses and promotion of repair responses to inflammatory stimuli. J. Immunol. 182, 5024–5031 (2009).
Appleton, C. T. et al. Forced mobilization accelerates pathogenesis: characterization of a preclinical surgical model of osteoarthritis. Arthritis Res. Ther. 9, R13 (2007).
Appleton, C. T. et al. Global analyses of gene expression in early experimental osteoarthritis. Arthritis Rheum. 56, 1854–1868 (2007).
Little, C. B. et al. Matrix metalloproteinase 13-deficient mice are resistant to osteoarthritic cartilage erosion but not chondrocyte hypertrophy or osteophyte development. Arthritis Rheum. 60, 3723–3733 (2009).
Fuerst, M. et al. Calcification of articular cartilage in human osteoarthritis. Arthritis Rheum. 60, 2694–2703 (2009).
Serra, R. et al. Expression of a truncated, kinase-defective TGF-β type II receptor in mouse skeletal tissue promotes terminal chondrocyte differentiation and osteoarthritis. J. Cell. Biol. 139, 541–552 (1997).
Yang, X. et al. TGF-beta/Smad3 signals repress chondrocyte hypertrophic differentiation and are required for maintaining articular cartilage. J. Cell. Biol. 153, 35–46 (2001).
Finnson, K. W. et al. ALK1 opposes ALK5/Smad3 signaling and expression of extracellular matrix components in human chondrocytes. J. Bone Miner. Res. 23, 896–906 (2008).
Blaney Davidson, E. N. et al. Increase in ALK1/ALK5 ratio as a cause for elevated MMP-13 expression in osteoarthritis in humans and mice. J. Immunol. 182, 7937–7945 (2009).
van der Kraan, P. M, Goumans, M. J., Blaney Davidson, E. & Ten Dijke, P. Age-dependent alteration of TGF-β signalling in osteoarthritis. Cell Tissue Res. http://dx/doi.org/10.1007/s00441-011-1194-6.
Cecil, D. L. et al. Inflammation-induced chondrocyte hypertrophy is driven by receptor for advanced glycation end products. J. Immunol. 175, 8296–8302 (2005).
Johnson, K. A. et al. Distinct transglutaminase 2-independent and transglutaminase 2-dependent pathways mediate articular chondrocyte hypertrophy. J. Biol. Chem. 278, 18824–18832 (2003).
Merz, D. et al. IL-8/CXCL8 and growth-related oncogene alpha/CXCL1 induce chondrocyte hypertrophic differentiation. J. Immunol. 171, 4406–4415 (2003).
James, C. G. et al. Microarray analyses of gene expression during chondrocyte differentiation identifies novel regulators of hypertrophy. Mol. Biol. Cell 16, 5316–5333 (2005).
Stanton, L. A., Underhill, T. M. & Beier, F. MAP kinases in chondrocyte differentiation. Dev. Biol. 263, 165–175 (2003).
Stanton, L. A. et al. p38 MAP kinase signalling is required for hypertrophic chondrocyte differentiation. Biochem. J. 378, 53–62 (2004).
Ehlen, H. W., Buelens, L. A. & Vortkamp, A. Hedgehog signaling in skeletal development. Birth Defects Res. C Embryo Today 78, 267–279 (2006).
Lin, A. C. et al. Modulating hedgehog signaling can attenuate the severity of osteoarthritis. Nat. Med. 15, 1421–1425 (2009).
Tchetina, E. V. et al. Chondrocyte hypertrophy can be induced by a cryptic sequence of type II collagen and is accompanied by the induction of MMP-13 and collagenase activity: implications for development and arthritis. Matrix Biol. 26, 247–258 (2007).
Kamekura, S. et al. Contribution of runt-related transcription factor 2 to the pathogenesis of osteoarthritis in mice after induction of knee joint instability. Arthritis Rheum. 54, 2462–2470 (2006).
Kawaguchi, H. Endochondral ossification signals in cartilage degradation during osteoarthritis progression in experimental mouse models. Mol. Cells 25, 1–6 (2008).
Hirata, M. et al. C/EBPβ Promotes transition from proliferation to hypertrophic differentiation of chondrocytes through transactivation of p57Kip2. PLoS ONE 4, e4543 (2009).
Tsuchimochi, K. et al. GADD45β enhances Col10a1 transcription via the MTK1/MKK3/6/p38 axis and activation of C/EBPβ-TAD4 in terminally differentiating chondrocytes. J. Biol. Chem. 285, 8395–8407 (2010).
Yang, S. et al. Hypoxia-inducible factor-2α is a catabolic regulator of osteoarthritic cartilage destruction. Nat. Med. 16, 687–693 (2010).
Saito, T. et al. Transcriptional regulation of endochondral ossification by HIF-2α during skeletal growth and osteoarthritis development. Nat. Med. 16, 678–686 (2010).
Araldi, E. et al. Lack of HIF-2α in limb bud mesenchyme causes a modest and transient delay of endochondral bone development. Nat. Med. 17, 25–26 (2011).
Nakajima, M. et al. Replication studies in various ethnic populations do not support the association of the HIF-2α SNP rs17039192 with knee osteoarthritis. Nat. Med. 17, 26–27 (2011).
Acknowledgements
A. A. Pitsillides is supported in his work by grant funding from Arthritis Research UK and Biotechnology and Biological Sciences Research Council. F. Beier is supported by a Canada Research Chair Award and operating funds from the Canadian Institutes of Health Research (CIHR MOP 43,899, 86,574 and 106,516).
Author information
Authors and Affiliations
Contributions
Both authors contributed equally to researching, discussing, writing, editing and reviewing this manuscript.
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing financial interests.
Rights and permissions
About this article
Cite this article
Pitsillides, A., Beier, F. Cartilage biology in osteoarthritis—lessons from developmental biology. Nat Rev Rheumatol 7, 654–663 (2011). https://doi.org/10.1038/nrrheum.2011.129
Published:
Issue Date:
DOI: https://doi.org/10.1038/nrrheum.2011.129
This article is cited by
-
Inhibition of TRADD ameliorates chondrocyte necroptosis and osteoarthritis by blocking RIPK1-TAK1 pathway and restoring autophagy
Cell Death Discovery (2023)
-
Circulating miR-146b and miR-27b are efficient biomarkers for early diagnosis of Equidae osteoarthritis
Scientific Reports (2023)
-
Autologous chondrocyte implantation provides good long-term clinical results in the treatment of knee osteoarthritis: a systematic review
Knee Surgery, Sports Traumatology, Arthroscopy (2023)
-
Deletion of DYRK1A Accelerates Osteoarthritis Progression Through Suppression of EGFR-ERK Signaling
Inflammation (2023)
-
MiR-99a alleviates apoptosis and extracellular matrix degradation in experimentally induced spine osteoarthritis by targeting FZD8
BMC Musculoskeletal Disorders (2022)