Reseach for cell-cell communication in bone remodeling and differentiation of osteoblast and osteoclast

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In the process of bone remodeling, the local calcium (Ca^<2+>) concentration at the resorption sites rises to as high as 40 mM and mononuclear cells appear at the resorptive sites at the end of a resorption phase. We obtained from the present study the evidence that high Ca^<2+> plays an important role in the appearance of mononuclear cells, followed by osteoblasts, at the resorptive sites and that mononuclear cells as well as high Ca^<2+> at the resorptive site also play an important role in the coupling of osteoblastic bone formation to osteoclastic bone resorption. The present sudy also demonstrated that an increase in extracellular Ca^<2+> concentration caused an increase in osteoblast proliferation directly through an increase in the production and secretion of insulin-like growth factor-1 (IGF-1) and indirectly via modulating the release of local facors of bone turnover from monocytes. The next project was to clarify whether calcitonin directly acts on osteoblasts as well as osteoclasts. Our study demonstrated that calcitonin directly acts on osteoblasts, followed by an increase in osteoblast proliferation and differentiation possiby through inducing c-fos gene expression and stimulating IGF-1 gene expression. Osteoblasts possess parathyroid hormone (PTH)-responsive dual signal transduction systems [cAMP-depindent protein kinase (PKA) and calcium/protein kinase C (Ca/PKC)]. In the present study, we demonstrated the direct involvement of PKA in the stimulation of bone resorption by PTH.Moreover, PTH possessed the ability to stimulate osteoclast differentiation through releasing the soluble factor from osteoblasts and this effect was exerted via these PTH-responsive dual signal transduction systems. On the other hand, there is evidence about the existence of PTH binding sites in osteoclast precursors. The present study demonstrated that hemopoietic blast cells derived from mouse spleen cells also possess PTH-responsive dual signal transducti