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ORIGINAL RESEARCH article

Front. Cell Dev. Biol.
Sec. Stem Cell Research
Volume 12 - 2024 | doi: 10.3389/fcell.2024.1511908
This article is part of the Research Topic Recent Advancements in Musculoskeletal Regenerative Medicine View all 3 articles

BMP9 induces postnatal zonal stratification of immature articular cartilage by reconfiguration of the existing collagen framework

Provisionally accepted
Ilyas Khan Ilyas Khan *Miles Anderson-Watters Miles Anderson-Watters
  • Swansea University Medical School, Swansea, United Kingdom

The final, formatted version of the article will be published soon.

    Articular cartilage lines bones in synovial joints and its main structural element, collagen, has an arcade-like arrangement that is produced from an initially random network around the time of puberty, in a process called postnatal maturation. This reshaping of the extracellular matrix is similar across all species and is critical for life-long cartilage strength and durability. Maturation is difficult to study because it ends at growth plate closure and in larger animals this can be months or years from the start of puberty. In this study we show growth factor bone morphogenetic protein-9 (BMP9) induces collagen remodelling in intact immature articular cartilage explants within 21 days, generating the characteristic arcade-like structure and zonal anisotropic architecture of adult cartilage. In explants exposed to BMP9, collagen fibrils underwent angular displacement from 19˚ to 78˚ with respect to the surface, cell density fell 1.77-fold and chondrons were significantly larger. Lack of labelling using anti-COL2¾m a marker of collagen turnover showed that the existing fibril network was restructured. We found stromelysin-1 (metalloproteinase-3, MMP3) gene expression was consistently upregulated whilst other MMPs transcript levels were unchanged or reduced. Remodelling was conditional upon proteoglycan turnover and inhibited using PD166973. These data suggest a possible mechanism whereby MMP3 depletes proteoglycan and depolymerises collagen fibrils enabling them to undergo spatial reorganisation driven by tissue swelling generated directional strain to align fibrils in an arcade-like pattern. The ability to induce tissue maturation brings closer tissue engineering of durable and functional cartilage for patients needing joint repair for diseases such as osteoarthritis.

    Keywords: Cartilage, postnatal maturation, Collagen, BMP9/GDF2, Arcades, stratification

    Received: 15 Oct 2024; Accepted: 04 Dec 2024.

    Copyright: © 2024 Khan and Anderson-Watters. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Ilyas Khan, Swansea University Medical School, Swansea, United Kingdom

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.