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

间充质祖细胞中的Sox9对其分化为软骨细胞具有重要作用，但其分化为软骨细胞后的功能尚未确定。为了更准确地研究Sox9在软骨细胞中的功能，我们在小鼠的软骨细胞分化过程中删除了Sox9基因。SOX9灭活灭活软骨细胞可导致细胞凋亡。分子分析表明，Sox9持续参与软骨细胞的分化，我们发现在缺乏SIK3的小鼠生长板软骨中，软骨细胞肥大明显延迟。需要SIK3将HDAC4锚定在胞浆中，从而释放MEF2C，MEF2C是软骨细胞肥大的关键促进剂，不受HDAC4在细胞核中的抑制。根据这些结果，我们得出结论，SIK3促进了软骨细胞在软骨形成和维持过程中的肥大

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