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

骨重塑及成骨细胞和破骨细胞分化中细胞间通讯的研究

• 批准号: 04671479
• 负责人: SUGIMOTO Toshitsugu
• 金额: $ 1.34万
• 依托单位: Kobe University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04671479/
• 关键词: Bone remodeling; Monocyte; Calcium; Insulin-like growth factor-1; Parathyroid hormone; Cacitonin; Bone morphogenetic protein; Differentiation; 骨リモデリング; 骨吸収; 骨芽細胞; 破骨細胞; 化学走化性

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

在骨重塑过程中，再吸收部位的局部钙(Ca 2+ )浓度升高至高达40mM，并且在再吸收阶段结束时，在再吸收部位出现单核细胞。我们从本研究中获得的证据表明，高Ca^<2+>在再吸收部位的单核细胞、其次是成骨细胞的出现中起着重要作用，并且单核细胞以及再吸收部位的高Ca^<2+>也在成骨细胞骨形成与破骨细胞骨吸收的耦合中发挥重要作用。本研究还证明，细胞外Ca^2+浓度的增加直接通过胰岛素样生长因子-1(IGF-1)的产生和分泌的增加以及通过调节单核细胞局部骨转换因子的释放间接引起成骨细胞增殖的增加。下一个项目是澄清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，然后通过诱导c-fos基因表达和刺激IGF-1基因表达来增加成骨细胞增殖和分化。成骨细胞拥有甲状旁腺激素 (PTH) 响应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，我们证明了 PKA 直接参与 PTH 刺激骨吸收。此外，PTH 具有通过成骨细胞释放可溶性因子刺激破骨细胞分化的能力，并且这种作用是通过这些 PTH 响应的双重信号转导系统发挥的。另一方面，有证据表明破骨细胞前体中存在 PTH 结合位点。本研究表明，源自小鼠脾细胞的造血母细胞也具有 PTH 响应性双重信号转导

项目成果

T.Sugimoto, T.Tsutsumi, Y.Fujii, M.Kawakatsu, H.Negishi, M.C.Lee, Ken-Sung Tsai, M.Fukase, T.Fujita: "Comparison of bone mineral content among Japanese, Koreans and Tqiwanese assessed by dual photon absorptiometry." J Bone Miner Res. 7. 153-159 (1992)

T.Sugimoto、T.Tsutsumi、Y.Fujii、M.Kawakatsu、H.Negishi、M.C.Lee、Ken-Sung Tsai、M.Fukase、T.Fujita：“日本人、韩国人和提吉瓦人的骨矿物质含量比较

Toshitsugu Sugimoto: "Effects of high calcium concentration on the functions and interactions of osteoblastic cells and monocytes and on the formation of osteoclast-like cells." J Bone Miner Res. 8. 1445-1452 (1993)

Toshitsugu Sugimoto：“高钙浓度对成骨细胞和单核细胞的功能和相互作用以及破骨细胞样细胞形成的影响。”

Toshitsugu Sugimoto: "Second messenger signaling in the regulation of cytosolic pH and DNA synthesis by parathyroid hormone(PTH)and PTH-related peptide mosteoblastic osteosarcoma cells." J Cell Physiol. 152. 28-34 (1992)

Toshitsugu Sugimoto：“甲状旁腺激素 (PTH) 和 PTH 相关肽成骨细胞骨肉瘤细胞调节胞质 pH 和 DNA 合成的第二信使信号传导。”

T.Sugimoto, M.Kanatani, H.Kaji, T.Yamaguchi, M.Fukase, K.Chihara: "Second messenger signaling of PTH- and PTHRP-stimulated osteoclast-like cell formation from hemopoietic blast cells." Am J Physiol. 265. E367-E373 (1993)

T.Sugimoto、M.Kanatani、H.Kaji、T.Yamaguchi、M.Fukase、K.Chihara：“PTH 和 PTHRP 刺激造血母细胞形成破骨细胞样细胞的第二信使信号传导。”

H.Kaji, T.Sugimoto, M.Kanatani, A.Miyauchi, T.Kimura, S.Sakakiibara, M.Fukase, K.Fukase, K.Chihara: "Carboxyl-terminal parathyroid hormone tragments stimulate osteoclast-like cell fromation and osteoclastic activity." Endocrinology. (in press).

H.Kaji、T.Sugimoto、M.Kanatani、A.Miyauchi、T.Kimura、S.Sakakiibara、M.Fukase、K.Fukase、K.Chihara：“羧基末端甲状旁腺激素片段刺激破骨细胞样细胞形成和