Cartilage Biology in Osteoarthritis--lessons from Developmental Biology

Overview

Journal Nat Rev Rheumatol

Specialty Rheumatology

Date 2011 Sep 28

PMID 21947178

Citations 103

Authors

Andrew A Pitsillides

Frank Beier

Affiliations

Soon will be listed here.

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.

Citing Articles

Inhibition of KDM6B prevents osteoarthritis by blocking growth plate-like H3K27me3 loss in bivalent genes.

Du H, Zhang Y, Yu X, You X, Wu D, Du Z Sci China Life Sci. 2025; .

PMID: 39969745 DOI: 10.1007/s11427-024-2676-y.

Targeting Chondrocyte Hypertrophy as Strategies for the Treatment of Osteoarthritis.

Dong D, Jin G Bioengineering (Basel). 2025; 12(1).

PMID: 39851351 PMC: 11760869. DOI: 10.3390/bioengineering12010077.

Development of a Microphysiological Cartilage-on-Chip Platform for Dynamic Biomechanical Stimulation of Three-Dimensional Encapsulated Chondrocytes in Agarose Hydrogels.

Peitso V, Sarmadian Z, Henriques J, Lauwers E, Paggi C, Mobasheri A Curr Protoc. 2024; 4(12):e70079.

PMID: 39697087 PMC: 11656284. DOI: 10.1002/cpz1.70079.

The methylomic landscape of human articular cartilage development contains epigenetic signatures of osteoarthritis risk.

McDonnell E, Orr S, Barter M, Rux D, Brumwell A, Wrobel N Am J Hum Genet. 2024; 111(12):2756-2772.

PMID: 39579763 PMC: 11639090. DOI: 10.1016/j.ajhg.2024.10.017.

Primary cartilage transcriptional signatures reflect cell-type-specific molecular pathways underpinning osteoarthritis.

Katsoula G, Lawrence J, Arruda A, Tutino M, Balogh P, Southam L Am J Hum Genet. 2024; 111(12):2735-2755.

PMID: 39579762 PMC: 11639091. DOI: 10.1016/j.ajhg.2024.10.019.

References

Yang S, Kim J, Ryu J, Oh H, Chun C, Kim B . Hypoxia-inducible factor-2alpha is a catabolic regulator of osteoarthritic cartilage destruction. Nat Med. 2010; 16(6):687-93. DOI: 10.1038/nm.2153. View

Goff D, Tabin C . Analysis of Hoxd-13 and Hoxd-11 misexpression in chick limb buds reveals that Hox genes affect both bone condensation and growth. Development. 1997; 124(3):627-36. DOI: 10.1242/dev.124.3.627. View

Blom A, Brockbank S, van Lent P, van Beuningen H, Geurts J, Takahashi N . Involvement of the Wnt signaling pathway in experimental and human osteoarthritis: prominent role of Wnt-induced signaling protein 1. Arthritis Rheum. 2009; 60(2):501-12. DOI: 10.1002/art.24247. View

Otsuki S, Hanson S, Miyaki S, Grogan S, Kinoshita M, Asahara H . Extracellular sulfatases support cartilage homeostasis by regulating BMP and FGF signaling pathways. Proc Natl Acad Sci U S A. 2010; 107(22):10202-7. PMC: 2890424. DOI: 10.1073/pnas.0913897107. View

Williams R, Khan I, Richardson K, Nelson L, McCarthy H, Analbelsi T . Identification and clonal characterisation of a progenitor cell sub-population in normal human articular cartilage. PLoS One. 2010; 5(10):e13246. PMC: 2954799. DOI: 10.1371/journal.pone.0013246. View

Stanton L, Underhill T, Beier F . MAP kinases in chondrocyte differentiation. Dev Biol. 2003; 263(2):165-75. DOI: 10.1016/s0012-1606(03)00321-x. View

Pitsillides A, Archer C, Prehm P, Bayliss M, Edwards J . Alterations in hyaluronan synthesis during developing joint cavitation. J Histochem Cytochem. 1995; 43(3):263-73. DOI: 10.1177/43.3.7868856. View

Brunet L, McMahon J, McMahon A, Harland R . Noggin, cartilage morphogenesis, and joint formation in the mammalian skeleton. Science. 1998; 280(5368):1455-7. DOI: 10.1126/science.280.5368.1455. View

Clarkin C, Allen S, Kuiper N, Wheeler B, Wheeler-Jones C, Pitsillides A . Regulation of UDP-glucose dehydrogenase is sufficient to modulate hyaluronan production and release, control sulfated GAG synthesis, and promote chondrogenesis. J Cell Physiol. 2010; 226(3):749-61. DOI: 10.1002/jcp.22393. View

10.

Dy P, Smits P, Silvester A, Penzo-Mendez A, Dumitriu B, Han Y . Synovial joint morphogenesis requires the chondrogenic action of Sox5 and Sox6 in growth plate and articular cartilage. Dev Biol. 2010; 341(2):346-59. PMC: 2862098. DOI: 10.1016/j.ydbio.2010.02.024. View

11.

Hyde G, Dover S, Aszodi A, Wallis G, Boot-Handford R . Lineage tracing using matrilin-1 gene expression reveals that articular chondrocytes exist as the joint interzone forms. Dev Biol. 2007; 304(2):825-33. PMC: 2795868. DOI: 10.1016/j.ydbio.2007.01.026. View

12.

Ehlen H, Buelens L, Vortkamp A . Hedgehog signaling in skeletal development. Birth Defects Res C Embryo Today. 2006; 78(3):267-79. DOI: 10.1002/bdrc.20076. View

13.

Blaney Davidson E, Remst D, Vitters E, van Beuningen H, Blom A, Goumans M . Increase in ALK1/ALK5 ratio as a cause for elevated MMP-13 expression in osteoarthritis in humans and mice. J Immunol. 2009; 182(12):7937-45. DOI: 10.4049/jimmunol.0803991. View

14.

Zhu M, Tang D, Wu Q, Hao S, Chen M, Xie C . Activation of beta-catenin signaling in articular chondrocytes leads to osteoarthritis-like phenotype in adult beta-catenin conditional activation mice. J Bone Miner Res. 2008; 24(1):12-21. PMC: 2640321. DOI: 10.1359/jbmr.080901. View

15.

Tchetina E, Squires G, Robin Poole A . 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. 2005; 32(5):876-86. View

16.

Edwards J, Wilkinson L, Jones H, Soothill P, Henderson K, Worrall J . The formation of human synovial joint cavities: a possible role for hyaluronan and CD44 in altered interzone cohesion. J Anat. 1994; 185 ( Pt 2):355-67. PMC: 1166765. View

17.

Tabin C, Wolpert L . Rethinking the proximodistal axis of the vertebrate limb in the molecular era. Genes Dev. 2007; 21(12):1433-42. DOI: 10.1101/gad.1547407. View

18.

Kannu P, Bateman J, Randle S, Cowie S, du Sart D, McGrath S . Premature arthritis is a distinct type II collagen phenotype. Arthritis Rheum. 2010; 62(5):1421-30. DOI: 10.1002/art.27354. View

19.

Lovinescu I, Koyama E, Pacifici M . Roles of FGF-10 on the development of diathrodial limb joints. Penn Dent J (Phila). 2004; 103:5, 9. View

20.

Koyama E, Shibukawa Y, Nagayama M, Sugito H, Young B, Yuasa T . A distinct cohort of progenitor cells participates in synovial joint and articular cartilage formation during mouse limb skeletogenesis. Dev Biol. 2008; 316(1):62-73. PMC: 2373417. DOI: 10.1016/j.ydbio.2008.01.012. View