Work

Dynamic cell fate plasticity and tissue reintegration drive functional adult synovial joint regeneration after complete resection

Year: 2025

Type: article

Abstract: Adult mammalian synovial joints have limited regenerative capacity, where injuries heal with mechanically inferior fibrotic tissues. Here we developed a unilateral whole-joint resection model in adult zebrafish to advance our understanding of how to stimulate regrowth of native synovial joint tissues. Using a combination of microCT, histological, live imaging, and single-cell RNA sequencing (scRNAseq) approaches after complete removal of all joint tissues, we find de novo regeneration of articular cartilage, ligament, and synovium into a functional joint. Clonal lineage tracing and scRNAseq implicate a multipotent, neural crest-derived population in the adult skeleton as a cell source for these regenerating tissues. Together, our findings reveal latent molecular and cellular programs within the adult skeleton that are deployed to regenerate a complex joint with lubricated articular cartilage. Joint injury and disease are leading causes of disability, with mammalian joints exhibiting poor regenerative capacity. Here the authors showed that after loss of a whole joint, adult zebrafish regenerate de novo articular cartilage, ligament, and synovium into a complex joint organ.

Source: Nature Communications

DOI: 10.1038/s41467-025-63596-8