Chondrocyte Proliferation and Differentiation

The skeletal elements of the axial and appendicular skeleton are preformed as cartilage templates by a mechanism called endochondral ossification. During this process, a cartilage template is formed in which chondrocytes proliferate and differentiate into hypertrophic chondrocytes and are gradually replaced by bone. Postnatally, remnants of embryonic chondrocytes remain in a restricted domain between the ossified regions of the bones forming the growth plate. The coordinated proliferation and differentiation of chondrocytes ensures the continuous elongation of the epiphyseal growth plates. The sequential changes between proliferation and differentiation are tightly regulated by secreted growth factors, which activate chondrocyte-specific transcription factors. Transcription factors that play critical roles in regulating cell type-specific gene expression include SOX9, GLI2/3 and RUNX2. This review will outline recent advances in the analysis of the complex transcriptional network that regulates distinct steps of chondrocyte differentiation.