SOX9 and the many facets of its regulation in the chondrocyte lineage.
SOX9 and the many facets of its regulation in the chondrocyte lineage.
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DOI：
10.1080/03008207.2016.1183667
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发表时间：
2017-01
影响因子：
2.9
通讯作者：
Dvir-Ginzberg M
中科院分区：
文献类型：
--
作者：
Lefebvre V;Dvir-Ginzberg M
SOX 9是发育和成年软骨中的关键转录因子。其基因由多能骨骼祖细胞表达，并在整个软骨细胞分化过程中具有活性。虽然它在软骨生长板中的肥大软骨细胞中被抑制，但它在健康关节软骨的永久软骨细胞中保持终生表达。SOX 9是软骨形成所必需的：它确保软骨细胞谱系定型，促进细胞存活，并转录激活许多软骨特异性结构成分和调节因子的基因。由于SOX 9内部和周围的杂合突变被证明会导致称为Campomelic发育不良的严重骨骼畸形综合征，世界各地的研究人员一直在努力破译SOX 9在软骨形成中的作用和调节的许多方面。我们了解的越多，我们就越能意识到SOX 9发挥其功能的分子网络的复杂性，并在其基因、RNA和蛋白质水平上受到调控，我们就越能衡量知识中存在的许多空白。与此同时，新技术不断为我们提供更多的手段，进一步推动知识的前沿。必须进行研究工作以填补这些空白，并更好地了解和治疗许多类型的软骨疾病，其中SOX 9具有或可能具有关键作用。这些疾病包括软骨发育不良和软骨变性疾病，即骨关节炎，一种流行且仍然无法治愈的关节疾病。我们在这里回顾了软骨细胞谱系中SOX 9作用和调节的知识现状，并为未来的基础和转化研究项目提出了新的方向。
SOX9 is a pivotal transcription factor in developing and adult cartilage. Its gene is expressed from the multipotent skeletal progenitor cells and is active throughout chondrocyte differentiation. While it is repressed in hypertrophic chondrocytes in cartilage growth plates, it remains expressed throughout life in permanent chondrocytes of healthy articular cartilage. SOX9 is required for chondrogenesis: it secures chondrocyte lineage commitment, promotes cell survival, and transcriptionally activates the genes for many cartilage-specific structural components and regulatory factors. Since heterozygous mutations within and around SOX9 were shown to cause the severe skeletal malformation syndrome called Campomelic Dysplasia, researchers around the world have worked assiduously to decipher the many facets of SOX9 actions and regulation in chondrogenesis. The more we learn, the more we realize the complexity of the molecular networks in which SOX9 fulfills its functions and is regulated at the levels of its gene, RNA and protein, and the more we measure the many gaps remaining in knowledge. At the same time, new technologies keep giving us more means to push further the frontiers of knowledge. Research efforts must be pursued to fill these gaps and to better understand and treat many types of cartilage diseases in which SOX9 has or could have a critical role. These diseases include chondrodysplasias and cartilage degeneration diseases, namely osteoarthritis, a prevalent and still incurable joint disease. We here review the current state of knowledge of SOX9 actions and regulation in the chondrocyte lineage, and propose new directions for future fundamental and translational research projects.