Massengale M, Massengale JL, Benson CR, Baryawno N, Oki T, Steinhauser ML, Wang A, Balani D, Oh LS, Randolph MA, Gill TJ, Kronenberg HM, Scadden DT. 2023. Adult Prg4+ progenitors repair long-term articular cartilage wounds in vivo. JCI insight. 8(17). Pubmed: 37681409 DOI:10.1172/jci.insight.167858


The identity and origin of the stem/progenitor cells for adult joint cartilage repair remain unknown, impeding therapeutic development. Simulating the common therapeutic modality for cartilage repair in humans, i.e., full-thickness microfracture joint surgery, we combined the mouse full-thickness injury model with lineage tracing and identified a distinct skeletal progenitor cell type enabling long-term (beyond 7 days after injury) articular cartilage repair in vivo. Deriving from a population with active Prg4 expression in adulthood while lacking aggrecan expression, these progenitors proliferate, differentiate to express aggrecan and type II collagen, and predominate in long-term articular cartilage wounds, where they represent the principal repair progenitors in situ under native repair conditions without cellular transplantation. They originate outside the adult bone marrow or superficial zone articular cartilage. These findings have implications for skeletal biology and regenerative medicine for joint injury repair.

Related Faculty

Photo of David Scadden

David Scadden’s laboratory is dedicated to discovering the principles governing blood cell production, with the ultimate goal of guiding the development of therapies for blood disorders and cancer.

Search Menu