Ohata Yasuhisa, Ozono Keiichi
Department of Pediatrics, Osaka University Graduate School of Medicine, Japan.
Clin Calcium. 2014 Apr;24(4):501-8.
Osteoblasts and osteocytes originate from pluripotent mesenchymal stem cells. Mesenchymal stem cells commit to osteogenic lineage and differentiate into mature osteoblasts and osteocytes through osteoprogenitor cells and preosteoblasts in response to multiple stimuli. The osteoblast commitment, differentiation, and functions are governed by several transcription factors. Among these transcription factors, runt-related transcription factor 2 (Runx2) is a crucial factor in osteoblast differentiation and controls bone formation. Differentiation toward these osteogenic lineage is controlled by a multitude of cytokines including WNTs, bone morphogenetic protein (BMP) , transforming growth factor-β (TGF-β) , hedgehog, parathyroid hormone (PTH) /parathyroid hormone related protein (PTHrP) , insulin-like growth factor-1 (IGF-1) , fibroblast growth factor (FGF) , and Notch. Although regulation of Runx2 activity is a point of convergence of many of the signal transduction routes, there is also a high degree of cross-talk between these pathways. Thus, the combined action of the signal transduction pathways induced by some cytokines determines the commitment and differentiation of mesenchymal stem cells toward the osteogenic lineage.
成骨细胞和骨细胞起源于多能间充质干细胞。间充质干细胞响应多种刺激,定向分化为成骨谱系,并通过骨祖细胞和前成骨细胞分化为成熟的成骨细胞和骨细胞。成骨细胞的定向分化、分化过程及功能受多种转录因子调控。在这些转录因子中, runt相关转录因子2(Runx2)是成骨细胞分化的关键因子,控制着骨形成。向这些成骨谱系的分化受多种细胞因子调控,包括WNTs、骨形态发生蛋白(BMP)、转化生长因子-β(TGF-β)、刺猬因子、甲状旁腺激素(PTH)/甲状旁腺激素相关蛋白(PTHrP)、胰岛素样生长因子-1(IGF-1)、成纤维细胞生长因子(FGF)和Notch。尽管Runx2活性的调节是许多信号转导途径的交汇点,但这些途径之间也存在高度的相互作用。因此,某些细胞因子诱导的信号转导途径的联合作用决定了间充质干细胞向成骨谱系的定向分化和分化过程。