Controlled induction and targeted elimination of p16^INK4a-expressing chondrocytes in cartilage explant culture.

ABSTRACT: Cellular senescence is a phenotypic state that contributes to age-related diseases through the secretion of matrix-degrading and inflammatory molecules. An emerging therapeutic strategy for osteoarthritis (OA) is to selectively eliminate senescent cells by initiating apoptosis. This study establishes a cartilage explant model of senescence induction and senolytic clearance using p16^Ink4a expression as a biomarker of senescence. Growth-factor stimulation of explants increased the expression of p16^Ink4a at both the mRNA and protein levels. Applying this culture system to cartilage from p16tdTom reporter mice (a knockin allele with tdTomato fluorescent protein regulated by the endogenous p16Ink4a promoter) demonstrated the emergence of a p16-high population that w

SUBMITTER: Sessions GA 

PROVIDER: S-EPMC6988852 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature