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<p>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.</p>

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年9月29日

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  • Maria Blumenkrantz,
  • Felicia Woron,
  • Ernesto Gagarin,
  • Everett Weinstein,
  • Maryam H. Kamel,
  • Leonardo Campos,
  • Agnieszka Geras,
  • Troy Anderson,
  • Julia Mo,
  • Desmarie Sherwood,
  • Maya Gwin,
  • Bianca Dumitrascu,
  • Nadeen O. Chahine,
  • Joanna Smeeton

摘要

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.