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

Miles Anderson-Watters, Ilyas Khan Orcid Logo

Frontiers in Cell and Developmental Biology, Volume: 12, Start page: 1511908

Swansea University Authors: Miles Anderson-Watters, Ilyas Khan Orcid Logo

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DOI (Published version): 10.3389/fcell.2024.1511908

Abstract

Articular cartilage lines bones in synovial joints, and its main structural element, collagen, has an arcade-like arrangement formed from an initially random network in a process called postnatal maturation. This reshaping of the extracellular matrix is similar across all species and is critical for...

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Published in: Frontiers in Cell and Developmental Biology
ISSN: 2296-634X
Published: Frontiers Media SA 2025
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URI: https://cronfa.swan.ac.uk/Record/cronfa68558
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This reshaping of the extracellular matrix is similar across all species and is critical for the lifelong strength and durability of cartilage. Collagen remodelling during maturation is difficult to study because it spans a period of time between birth and puberty, and in larger animals this can be months or years. In this study, we show that 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&#xB0; to 78&#xB0; with respect to the surface, cell density decreased 1.77-fold, and chondrons were significantly larger. The absence of labelling with anti-COL2&#xBE;m, a marker of collagen turnover, showed that the existing fibril network was restructured. 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spelling 2025-01-30T15:27:12.8570540 v2 68558 2024-12-12 BMP9 induces postnatal zonal stratification of immature articular cartilage by reconfiguration of the existing collagen framework 4c4fcb21b9ccf0fd5e5395005ae3d72d Miles Anderson-Watters Miles Anderson-Watters true false 2536d955ff70e7b77063a8efe9103161 0000-0002-3886-1987 Ilyas Khan Ilyas Khan true false 2024-12-12 MEDS Articular cartilage lines bones in synovial joints, and its main structural element, collagen, has an arcade-like arrangement formed from an initially random network in a process called postnatal maturation. This reshaping of the extracellular matrix is similar across all species and is critical for the lifelong strength and durability of cartilage. Collagen remodelling during maturation is difficult to study because it spans a period of time between birth and puberty, and in larger animals this can be months or years. In this study, we show that 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 decreased 1.77-fold, and chondrons were significantly larger. The absence of labelling with anti-COL2¾m, a marker of collagen turnover, showed that the existing fibril network was restructured. We found that stromelysin-1 (metalloproteinase-3, MMP3) gene expression was consistently upregulated, whilst other MMP transcript levels were unchanged or reduced. Remodelling was dependent on proteoglycan turnover and could be inhibited using PD166973. These data suggest a possible mechanism whereby MMP3 induces proteoglycan turnover and depolymerises collagen fibrils enabling them to undergo spatial reorganisation. This process may be driven by tissue swelling, which generates directional strain to align fibrils into an arcade-like pattern. The ability to induce tissue maturation advances the potential for engineering durable and functional cartilage for patients requiring joint repair due to diseases such as osteoarthritis. Journal Article Frontiers in Cell and Developmental Biology 12 1511908 Frontiers Media SA 2296-634X cartilage, postnatal maturation, collagen, BMP9/GDF2, Benninghoff arcades, zonal stratification 28 1 2025 2025-01-28 10.3389/fcell.2024.1511908 COLLEGE NANME Medical School COLLEGE CODE MEDS Swansea University External research funder(s) paid the OA fee (includes OA grants disbursed by the Library) IK would like to acknowledge funding from the Medical Research Council United Kingdom (MR/V027670/1) and EPSRC (EP/S014306/1) for this study. 2025-01-30T15:27:12.8570540 2024-12-12T14:12:20.8752708 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Biomedical Science Miles Anderson-Watters 1 Ilyas Khan 0000-0002-3886-1987 2 68558__33450__6a8ab9e531a04278b5ab35d78124cb9b.pdf 68558.VOR.pdf 2025-01-30T15:24:46.3760622 Output 5483513 application/pdf Version of Record true © 2025 Anderson-Watters and Khan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). true eng https://creativecommons.org/licenses/by/4.0/
title BMP9 induces postnatal zonal stratification of immature articular cartilage by reconfiguration of the existing collagen framework
spellingShingle BMP9 induces postnatal zonal stratification of immature articular cartilage by reconfiguration of the existing collagen framework
Miles Anderson-Watters
Ilyas Khan
title_short BMP9 induces postnatal zonal stratification of immature articular cartilage by reconfiguration of the existing collagen framework
title_full BMP9 induces postnatal zonal stratification of immature articular cartilage by reconfiguration of the existing collagen framework
title_fullStr BMP9 induces postnatal zonal stratification of immature articular cartilage by reconfiguration of the existing collagen framework
title_full_unstemmed BMP9 induces postnatal zonal stratification of immature articular cartilage by reconfiguration of the existing collagen framework
title_sort BMP9 induces postnatal zonal stratification of immature articular cartilage by reconfiguration of the existing collagen framework
author_id_str_mv 4c4fcb21b9ccf0fd5e5395005ae3d72d
2536d955ff70e7b77063a8efe9103161
author_id_fullname_str_mv 4c4fcb21b9ccf0fd5e5395005ae3d72d_***_Miles Anderson-Watters
2536d955ff70e7b77063a8efe9103161_***_Ilyas Khan
author Miles Anderson-Watters
Ilyas Khan
author2 Miles Anderson-Watters
Ilyas Khan
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container_title Frontiers in Cell and Developmental Biology
container_volume 12
container_start_page 1511908
publishDate 2025
institution Swansea University
issn 2296-634X
doi_str_mv 10.3389/fcell.2024.1511908
publisher Frontiers Media SA
college_str Faculty of Medicine, Health and Life Sciences
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hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
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hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Biomedical Science{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Biomedical Science
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description Articular cartilage lines bones in synovial joints, and its main structural element, collagen, has an arcade-like arrangement formed from an initially random network in a process called postnatal maturation. This reshaping of the extracellular matrix is similar across all species and is critical for the lifelong strength and durability of cartilage. Collagen remodelling during maturation is difficult to study because it spans a period of time between birth and puberty, and in larger animals this can be months or years. In this study, we show that 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 decreased 1.77-fold, and chondrons were significantly larger. The absence of labelling with anti-COL2¾m, a marker of collagen turnover, showed that the existing fibril network was restructured. We found that stromelysin-1 (metalloproteinase-3, MMP3) gene expression was consistently upregulated, whilst other MMP transcript levels were unchanged or reduced. Remodelling was dependent on proteoglycan turnover and could be inhibited using PD166973. These data suggest a possible mechanism whereby MMP3 induces proteoglycan turnover and depolymerises collagen fibrils enabling them to undergo spatial reorganisation. This process may be driven by tissue swelling, which generates directional strain to align fibrils into an arcade-like pattern. The ability to induce tissue maturation advances the potential for engineering durable and functional cartilage for patients requiring joint repair due to diseases such as osteoarthritis.
published_date 2025-01-28T05:22:17Z
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