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

在骨重建过程中，吸收部位的局部钙离子浓度高达40 mM，在吸收阶段结束时，吸收部位出现单核细胞。我们从本研究中得到的证据表明，在骨吸收部位，高钙对单个核细胞的出现起重要作用，其次是成骨细胞；在吸收部位，单核细胞和高钙在成骨细胞性骨形成和破骨细胞性骨吸收的偶联中也起重要作用。本研究还表明，细胞外钙离子浓度的增加直接通过增加胰岛素样生长因子-1(IGF-1)的产生和分泌而促进成骨细胞的增殖，间接地通过调节单核细胞释放局部骨转换因子来促进成骨细胞的增殖。下一个项目是阐明降钙素是否直接作用于成骨细胞和破骨细胞。我们的研究表明，降钙素直接作用于成骨细胞，可能通过诱导c-fos基因表达和刺激IGF-1基因表达而促进成骨细胞的增殖和分化。成骨细胞具有甲状旁腺激素(PTH)应答的双重信号转导系统[cAMP依赖性蛋白激酶(PKA)和钙/蛋白激酶C(Ca/PKC)]。在本研究中，我们证实了PKA直接参与了PTH刺激骨吸收的过程，并且PTH通过释放成骨细胞中的可溶性因子来刺激破骨细胞分化，这种作用是通过PTH反应的双重信号转导系统来实现的。另一方面，有证据表明破骨细胞前体中存在甲状旁腺素结合位点。本研究证实小鼠脾细胞来源的造血母细胞也具有甲状旁腺素反应的双重信号转导。

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