Lefebvre Véronique, Bhattaram Pallavi
Department of Cellular & Molecular Medicine, Orthopaedic and Rheumatologic Research Center, Cleveland Clinic Lerner Research Institute, 9500 Euclid Avenue, Cleveland, OH, 44195, USA.
Curr Osteoporos Rep. 2016 Feb;14(1):32-8. doi: 10.1007/s11914-016-0296-1.
The SOXC group of transcription factors, composed of SOX4, SOX11, and SOX12, has evolved to fulfill key functions in cell fate determination. Expressed in many types of progenitor/stem cells, including skeletal progenitors, SOXC proteins potentiate pathways critical for cell survival and differentiation. As skeletogenesis unfolds, SOXC proteins ensure cartilage primordia delineation by amplifying canonical WNT signaling and antagonizing the chondrogenic action of SOX9 in perichondrium and presumptive articular joint cells. They then ensure skeletal elongation by inducing growth plate formation via enabling non-canonical WNT signaling. Human studies have associated SOX4 with bone mineral density and fracture risk in osteoporotic patients, and SOX11 with Coffin-Siris, a syndrome that includes skeletal dysmorphism. Meanwhile, in vitro and mouse studies have suggested important cell-autonomous roles for SOXC proteins in osteoblastogenesis. We here review current knowledge and gaps in understanding of SOXC protein functions, with an emphasis on the skeleton and possible links to osteoporosis.
由SOX4、SOX11和SOX12组成的SOXC转录因子组已经进化到在细胞命运决定中发挥关键作用。SOXC蛋白在包括骨骼祖细胞在内的多种类型的祖细胞/干细胞中表达，增强对细胞存活和分化至关重要的信号通路。随着骨骼发生的展开，SOXC蛋白通过放大经典WNT信号和拮抗SOX9在软骨膜和假定关节细胞中的软骨生成作用来确保软骨原基的形成。然后，它们通过促进非经典WNT信号诱导生长板形成来确保骨骼延长。人体研究已将SOX4与骨质疏松症患者的骨密度和骨折风险相关联，将SOX11与科芬-西里斯综合征（一种包括骨骼畸形的综合征）相关联。同时，体外和小鼠研究表明SOXC蛋白在成骨细胞生成中具有重要的细胞自主作用。我们在此回顾当前对SOXC蛋白功能的认识和理解上的差距，重点是骨骼以及与骨质疏松症的可能联系。
