Regeneration of Jaw Joint Cartilage in Adult Zebrafish
The poor intrinsic repair capacity of mammalian joint cartilage likely contributes to the high incidence of arthritis worldwide. Adult zebrafish can regenerate many structures that show limited or no healing capacity in mammals, including the jawbone. To test whether zebrafish can also regenerate da...
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Frontiers Media S.A.
2022-01-01
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Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2021.777787/full |
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author | Joanna Smeeton Joanna Smeeton Joanna Smeeton Natasha Natarajan Troy Anderson Troy Anderson Kuo-Chang Tseng Peter Fabian J. Gage Crump |
author_facet | Joanna Smeeton Joanna Smeeton Joanna Smeeton Natasha Natarajan Troy Anderson Troy Anderson Kuo-Chang Tseng Peter Fabian J. Gage Crump |
author_sort | Joanna Smeeton |
collection | DOAJ |
description | The poor intrinsic repair capacity of mammalian joint cartilage likely contributes to the high incidence of arthritis worldwide. Adult zebrafish can regenerate many structures that show limited or no healing capacity in mammals, including the jawbone. To test whether zebrafish can also regenerate damaged joints, we developed a surgical injury model in which the zebrafish jaw joint is destabilized via transection of the major jaw joint ligament, the interopercular–mandibular (IOM). Unilateral transection of the IOM ligament in 1-year-old fish resulted in an initial reduction of jaw joint cartilage by 14 days, with full regeneration of joint cartilage by 28 days. Joint cartilage regeneration involves the re-entry of articular chondrocytes into the cell cycle and the upregulated expression of sox10, a marker of developing chondrocytes in the embryo that becomes restricted to a subset of joint chondrocytes in adults. Genetic ablation of these sox10-expressing chondrocytes shows that they are essential for joint cartilage regeneration. To uncover the potential source of new chondrocytes during joint regeneration, we performed single-cell RNA sequencing of the uninjured adult jaw joint and identified multiple skeletal, connective tissue, and fibroblast subtypes. In particular, we uncovered a joint-specific periosteal population expressing coch and grem1a, with the jaw joint chondrocytes marked by grem1a expression during regeneration. Our findings demonstrate the capacity of zebrafish to regenerate adult joint cartilage and identify candidate cell types that can be tested for their roles in regenerative response. |
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issn | 2296-634X |
language | English |
last_indexed | 2024-12-20T16:37:03Z |
publishDate | 2022-01-01 |
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series | Frontiers in Cell and Developmental Biology |
spelling | doaj.art-4a2781cac63048998f2bbb3c5e337c0f2022-12-21T19:33:08ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2022-01-01910.3389/fcell.2021.777787777787Regeneration of Jaw Joint Cartilage in Adult ZebrafishJoanna Smeeton0Joanna Smeeton1Joanna Smeeton2Natasha Natarajan3Troy Anderson4Troy Anderson5Kuo-Chang Tseng6Peter Fabian7J. Gage Crump8Department of Rehabilitation and Regenerative Medicine, Columbia Stem Cell Initiative, Columbia University Irving Medical Center, Columbia University, New York, NY, United StatesDepartment of Genetics and Development, Columbia Stem Cell Initiative, Columbia University Irving Medical Center, Columbia University, New York, NY, United StatesDepartment of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, United StatesDepartment of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, United StatesDepartment of Rehabilitation and Regenerative Medicine, Columbia Stem Cell Initiative, Columbia University Irving Medical Center, Columbia University, New York, NY, United StatesDepartment of Genetics and Development, Columbia Stem Cell Initiative, Columbia University Irving Medical Center, Columbia University, New York, NY, United StatesDepartment of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, United StatesDepartment of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, United StatesDepartment of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, United StatesThe poor intrinsic repair capacity of mammalian joint cartilage likely contributes to the high incidence of arthritis worldwide. Adult zebrafish can regenerate many structures that show limited or no healing capacity in mammals, including the jawbone. To test whether zebrafish can also regenerate damaged joints, we developed a surgical injury model in which the zebrafish jaw joint is destabilized via transection of the major jaw joint ligament, the interopercular–mandibular (IOM). Unilateral transection of the IOM ligament in 1-year-old fish resulted in an initial reduction of jaw joint cartilage by 14 days, with full regeneration of joint cartilage by 28 days. Joint cartilage regeneration involves the re-entry of articular chondrocytes into the cell cycle and the upregulated expression of sox10, a marker of developing chondrocytes in the embryo that becomes restricted to a subset of joint chondrocytes in adults. Genetic ablation of these sox10-expressing chondrocytes shows that they are essential for joint cartilage regeneration. To uncover the potential source of new chondrocytes during joint regeneration, we performed single-cell RNA sequencing of the uninjured adult jaw joint and identified multiple skeletal, connective tissue, and fibroblast subtypes. In particular, we uncovered a joint-specific periosteal population expressing coch and grem1a, with the jaw joint chondrocytes marked by grem1a expression during regeneration. Our findings demonstrate the capacity of zebrafish to regenerate adult joint cartilage and identify candidate cell types that can be tested for their roles in regenerative response.https://www.frontiersin.org/articles/10.3389/fcell.2021.777787/fulljointosteoarthritiszebrafishcartilageregeneration |
spellingShingle | Joanna Smeeton Joanna Smeeton Joanna Smeeton Natasha Natarajan Troy Anderson Troy Anderson Kuo-Chang Tseng Peter Fabian J. Gage Crump Regeneration of Jaw Joint Cartilage in Adult Zebrafish Frontiers in Cell and Developmental Biology joint osteoarthritis zebrafish cartilage regeneration |
title | Regeneration of Jaw Joint Cartilage in Adult Zebrafish |
title_full | Regeneration of Jaw Joint Cartilage in Adult Zebrafish |
title_fullStr | Regeneration of Jaw Joint Cartilage in Adult Zebrafish |
title_full_unstemmed | Regeneration of Jaw Joint Cartilage in Adult Zebrafish |
title_short | Regeneration of Jaw Joint Cartilage in Adult Zebrafish |
title_sort | regeneration of jaw joint cartilage in adult zebrafish |
topic | joint osteoarthritis zebrafish cartilage regeneration |
url | https://www.frontiersin.org/articles/10.3389/fcell.2021.777787/full |
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