Komori Toshihisa
Department of Molecular Tumor Biology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8588, Japan.
J Bone Miner Metab. 2025 Jan;43(1):33-38. doi: 10.1007/s00774-024-01551-1. Epub 2024 Oct 1.
Hedgehog and canonical Wnt signaling pathways and the transcription factors Runx2 and Sp7 are essential for osteoblast differentiation. Ihh is necessary for the commitment of perichondrial mesenchymal cells to Runx2 osteoprogenitors and for the formation of the bone collar and primary spongiosa. Runx2 is needed for osteoblast differentiation during both endochondral and intramembranous ossification. It regulates the commitment of mesenchymal cells to osteoblast-lineage cells and their proliferation by inducing the expression of Hedgehog, Fgf, Wnt, Pthlh signaling pathway genes, and Dlx5. The Runx2-induced expression of Fgfr2 and Fgfr3 is important for the proliferation of osteoblast-lineage cells. Runx2 induces Sp7 expression and Runx2 osteoprogenitors become Runx2Sp7 preosteoblasts. Runx2, Sp7, and canonical Wnt signaling induce the differentiation of preosteoblasts into osteoblasts. Canonical Wnt signaling, but not Sp7, enhances the proliferation of osteoblast-lineage cells. In mature osteoblasts, Runx2 plays an important role in the expression of major bone matrix protein genes, including Col1a1, Col1a2, Spp1, Ibsp, and Bglap/Bglap2. The canonical Wnt signaling pathway is also crucial for bone formation by mature osteoblasts. Sp7 is needed for osteocytes to acquire a sufficient number of processes and a reduction in these processes results in osteocyte apoptosis and cortical porosity.
刺猬信号通路和经典Wnt信号通路以及转录因子Runx2和Sp7对成骨细胞分化至关重要。Ihh对于软骨膜间充质细胞向Runx2成骨祖细胞的定向分化以及骨环和初级骨小梁的形成是必需的。在软骨内成骨和膜内成骨过程中，成骨细胞分化都需要Runx2。它通过诱导刺猬信号通路、Fgf、Wnt、Pthlh信号通路基因和Dlx5的表达，调节间充质细胞向成骨细胞系细胞的定向分化及其增殖。Runx2诱导的Fgfr2和Fgfr3表达对成骨细胞系细胞的增殖很重要。Runx2诱导Sp7表达，Runx2成骨祖细胞变成Runx2Sp7前成骨细胞。Runx2、Sp7和经典Wnt信号通路诱导前成骨细胞分化为成骨细胞。经典Wnt信号通路而非Sp7增强成骨细胞系细胞的增殖。在成熟成骨细胞中，Runx2在主要骨基质蛋白基因（包括Col1a1、Col1a2、Spp1、Ibsp和Bglap/Bglap2）的表达中起重要作用。经典Wnt信号通路对成熟成骨细胞的骨形成也至关重要。骨细胞获得足够数量的突起需要Sp7，这些突起减少会导致骨细胞凋亡和皮质骨孔隙率增加。
