SOX9 keeps growth plates and articular cartilage healthy by inhibiting chondrocyte dedifferentiation/osteoblastic redifferentiation

Significance Cartilage is essential in vertebrate development and adulthood. Cartilage growth plates ensure skeletal growth until closing at puberty, and articular cartilage ensures lifelong structural and functional integrity of joints. Chondrocytes build cartilage in development, governed by the transcription factor SOX9. Using mouse models and transcriptome profiling approaches, we show here that SOX9 also has key roles to maintain growth plates open postnatally and to protect adult articular cartilage from osteoarthritic degradation. In particular, SOX9 safeguards the lineage fate of chondrocytes by preventing their dedifferentiation into skeletogenic mesenchymal progenitors followed by redifferentiation into osteoblasts. These findings provide insights into cellular plasticity and its molecular control in developmental, physiological, and pathological processes within and beyond the skeletal system.