SOX9 in cartilage development and disease.

SOX9 is a pivotal transcription factor in chondrocytes, a lineage essential in skeletogenesis. Its mandatory role in transactivating many cartilage-specific genes is well established, whereas its pioneer role in lineage specification, which along with transactivation defines master transcription factors, remains to be better defined. Abundant, but yet incomplete evidence exists that intricate molecular networks control SOX9 activity during the multi-step chondrogenesis pathway. They include a highly modular genetic regulation, post-transcriptional and post-translational modifications, and varying sets of functional partners. Fully uncovering SOX9 actions and regulation is fundamental to explain mechanisms underlying many diseases that directly or indirectly affect SOX9 activities and to design effective disease treatments. We here review current knowledge, highlight recent discoveries, and propose new research directions to answer remaining questions.