Regeneration of Jaw Joint Cartilage in Adult Zebrafish

• Published in: Frontiers in cell and developmental biology Vol. 9; p. 777787
• Main Authors: Smeeton, Joanna, Natarajan, Natasha, Anderson, Troy, Tseng, Kuo-Chang, Fabian, Peter, Crump, J Gage
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 20.01.2022
• Subjects: cartilage; Cell and Developmental Biology; joint; osteoarthritis; regeneration; zebrafish; joint; zebrafish; regeneration; osteoarthritis; cartilage
• ISSN: 2296-634X; 2296-634X
• DOI: 10.3389/fcell.2021.777787

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 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 , a marker of developing chondrocytes in the embryo that becomes restricted to a subset of joint chondrocytes in adults. Genetic ablation of these -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 and , with the jaw joint chondrocytes marked by 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.