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  • Review Article
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Cartilage biology in osteoarthritis—lessons from developmental biology

A Correction to this article was published on 01 February 2013

This article has been updated

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

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Figure 1: Control of chondrogenesis during development.
Figure 2: Control of joint formation.
Figure 3: The mammalian growth plate.
Figure 4: Control of chondrocyte hypertrophy in osteoarthritis.
Figure 5: Developmental factors controlling articular chondrocyte behavior in OA.

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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.

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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).

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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

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