Regeneration of Jaw Joint Cartilage in Adult Zebrafish.
Publication Year:
2021
PubMed ID:
35127702
Funding Grants:
Public Summary:
Zebrafish, on the other hand, have a remarkable ability to regenerate various body structures that mammals cannot, such as their jawbone. To explore whether zebrafish can also regenerate damaged joints, researchers developed a surgical model that destabilized the zebrafish jaw joint. By cutting a specific ligament, the researchers observed an initial decrease in jaw joint cartilage at 14 days, followed by full cartilage regeneration at 28 days.They then identified a group of chondrocytes marked by the expression of the gene sox10 as essential for joint cartilage regeneration. Single-cell analysis of the jaw joint revealed different cell subtypes, including a population expressing coch and grem1a genes that play a vital role in jaw joint chondrocytes during regeneration. In summary, zebrafish have demonstrated the ability to regenerate adult joint cartilage, and this research has identified potential cell types that may contribute to this regenerative process.
Scientific Abstract:
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.