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首页> 外文期刊>Journal of Cellular Physiology >Calcitonin gene-related peptide (CGRP) inhibits apoptosis in human osteoblasts by beta-catenin stabilization.
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Calcitonin gene-related peptide (CGRP) inhibits apoptosis in human osteoblasts by beta-catenin stabilization.

机译：降钙素相关基因肽(CGRP怎样)抑制由β-连环蛋白在人类成骨细胞凋亡稳定。

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Transgenic mice over-expressing calcitonin gene-related peptide (CGRP) in osteoblasts have increased bone density due to increased bone formation, thus suggesting that CGRP plays a role in bone metabolism. In this study we determined the relationship between CGRP, the canonical Wnt signaling and apoptosis in human osteoblasts (hOBs) in consideration of the well-documented involvement of this pathway in bone cells. Primary cultures of hOBs were treated with CGRP 10(-8) M. Levels of beta-catenin, which is the cytoplasmic protein mediator of canonical Wnt signaling, and mRNA were determined. CGRP increases both the expression and the levels of cytoplasmic beta-catenin by binding to its receptor, as this effect is blocked by the antagonist CGRP(8-37). This facilitatory action on beta-catenin appears to be mediated by the inhibition of the enzyme GSK-3beta via protein kinase A (PKA) activation. GSK-3beta is a glycogen synthase kinase that, by phosphorylating beta-catenin, promotes its degradation by the proteosomal machinery. Moreover, the peptide is able to inhibit hOBs apoptosis stimulated by dexamethasone or by serum deprivation, possibly through the accumulation of beta-catenin, since the inhibitor of PKA activity H89 partially prevents the antiapoptotic effect of the peptide. In conclusion CGRP, released by nerve fibers, exerts its anabolic action on bone cells by stimulating canonical Wnt signaling and by inhibiting hOBs apoptosis, thus favoring local bone regeneration.
机译：转基因小鼠过度表达降钙素在成骨细胞相关基因肽(CGRP怎样)增加骨质密度将增加骨头形成,从而表明CGRP怎样扮演了一个角色在骨代谢。CGRP怎样的关系,规范Wnt在人类成骨细胞信号传导和细胞凋亡(滚铣刀)在证据充分的考虑这个途径参与骨细胞。滚铣刀的主要文化与CGRP怎样治疗10 (8) m .β-连环蛋白的水平,这是胞质蛋白规范化Wnt的中介信号,信使rna被确定。表达和水平的增加细胞质β-连环蛋白绑定到它受体,这种效应被阻塞的拮抗剂CGRP怎样(8-37)。在β-连环蛋白介导的通过蛋白抑制酶GSK-3beta激酶(PKA)激活。糖原合酶激酶,通过磷酸化β-连环蛋白,促进其降解变幻虫的机械。能够抑制滚铣刀凋亡刺激地塞米松或血清剥夺,可能通过β-连环蛋白的积累H89 PKA活性部分的抑制剂阻止了凋亡肽的影响。结论CGRP怎样,发布的神经纤维,发挥其对骨细胞合成代谢作用刺激规范Wnt信号抑制滚铣刀细胞凋亡,从而有利于当地骨再生。

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