骨芽細胞の分化と機能

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  • Differentiation and function of osteoblast
  • コツガ サイボウ ノ ブンカ ト キノウ

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Elucidation of molecular mechanisms controlling differentiation and function of osteoblasts is one of the major subjects in bone biology. Differentiation of cells is controlled at the level of transcription by various classes of transcription factors that have been identified through biochemical and genetic means. I showed an expression of rat osteocalcin gene in osteoblasts was mediated by basic helix-loop-helix (bHLH) type of transcription factors. Our study presented evidence that the E-box sequence, OCE1,and transcription factors interacting with this motif, are involved in osteoblast-specific osteocalcin gene transcription. Furthermore, I performed degenerate PCR cloning in order to identify cDNA clones encoding bHLH proteins expressed in osteoblasts. We got clones which sequences in the amplified region were homologous to the mouse twist-related HLH protein, Dermo-1. Dermo-1 mRNA was expressed in osteoblast-1ike cell lines, and could be involved in the osteoblastic differentiation in a negative manner. Current many studies using gene deficient mice revealed how osteoblast differentiation and bone remodeling are controlled through many other type of transcription factors, Cbfal and homeobox protein family. Karsenty et al. showed that Cbfal is necessary for differentiation of mesenchymal progenitor cells to osteoblasts, and Cbfal controls bone formation by differentiated osteoblasts. Extracellular signals including hormones, growth factors, or cytokines as well as their intracellular mediators regulate osteoblast function. In this paper, I reviewed new understandings of the molecular control of osteoblast differentiation and function.

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