Failed Cellular Surveillance Enables Pathogenic Matrix Deposition in a <i>COL2A1</i>-Related Osteoarthritis.

ABSTRACT: Mutations in the COL2A1 gene, encoding procollagen-II, cause various chondrodysplasias, including precocious osteoarthritis with mild spondyloepiphyseal dysplasia engendered by the p.Arg719Cys substitution. The molecular mechanisms underlying these disorders remain incompletely understood, largely owing to the absence of models faithfully recapitulating the human disease. Here, we developed an in vitro human cartilage model using isogenic induced pluripotent stem cell (iPSC) lines carrying either wild-type or Arg719Cys COL2A1. Directed differentiation into chondrocytes yielded cartilage tissues that were analyzed by immunohistochemistry, electron microscopy, SDS-PAGE, and RNA-sequencing. Tissues derived from Arg719Cys heterozygotes displayed a deficient matrix, closely

SUBMITTER: Yammine KM 

PROVIDER: S-EPMC11580999 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature