Dmrt2 promotes transition of endochondral bone formation by linking Sox9 and Runx2

Abstract Endochondral bone formation is fundamental for skeletal development. During this process, chondrocytes undergo multiple steps of differentiation and coordinated transition from a proliferating to hypertrophic stage, which critical advance Here, we identified the transcription factor Dmrt2 (double-sex mab-3 related 2) as Sox9-inducible gene that promotes chondrocyte hypertrophy in pre-hypertrophic chondrocytes. Epigenetic analysis further demonstrated Sox9 regulates expression through an active enhancer located 18 kb upstream enhancer’s chromatin status progressively activated differentiation. -knockout mice exhibited dwarf phenotype with delayed initiation hypertrophy. augmented including Ihh physical functional interaction Runx2. Furthermore, deficiency reduced Runx2-dependent expression. Our findings suggest sequential during endochondral coordinates transcriptional network between