Analysis of BMP-mediated cartilage formation anddifferentiation, and cartilage repair

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Sox9 in mesenchymal progenitors is important for their differentiation intochondrocytes, but its functions after differentiation into chondrocytes have not beendetermined. To investigate Sox9 function in chondrocytes precisely, we deleted Sox9genes after differentiation into chondrocytes in mice. Sox9 inactivation inchondrocytes resulted in apoptosis. Molecular analysis revealed that Sox9 sustainswhich are involved in chondrocyte differentiation, we discovered that chondrocytehypertrophy was markedly delayed in the growth plate cartilage in mice lacking saltinducible kinase 3 (SIK3). SIK3 was required for anchoring HDAC4 in the cytoplasm,thereby releasing MEF2C, a critical facilitator of chondrocyte hypertrophy, fromsuppression by HDAC4 in the nuclei. From these results, we concluded that SIK3facilitates chondrocyte hypertrophy during formation and maintenance of cartilage