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血钙促进生长板软骨细胞增殖的作用机理

Mechanism of Calcium Promoting the Proliferation of Growth Plate Chondrocytes
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摘要 脊椎动物生长发育需要足够外源Ca2+供给,而生长板软骨细胞在Ca2+代谢过程中发挥着重要作用。为了探究小鼠生长板软骨细胞IGF1R在Ca2+调节PTHrP/PTH1R信号传导途径中的作用机制,本研究通过Cre重组酶(Ad-Cre)的体外腺病毒感染,构建Igf1r诱导型基因敲除小鼠原代软骨细胞,借助Western blotting检测不同浓度Ca2+处理后关键蛋白因子PTHrP/PTH1R的表达情况。结果表明:高Ca2+能明显加快mGPC分化进程;Ca2+信号通过独立于IGF1R的信号传导来抑制PTH1R表达,并通过IGF1R依赖性途径抑制PTHrP表达,实现对生长板软骨细胞成熟分化的调节。小鼠生长板软骨细胞的分化速率取决于PTHrP/PTH1R与细胞外Ca2+信号传导之间相互作用的平衡状态。 The growth and development of vertebrates requires sufficient supply of exogenous Ca2+,and growth plate chondrocytes play a crucial role in Ca2+metabolism.To investigate the regulatory mechanism of IGF1R in mouse growth plate chondrocytes in Ca2+-mediated PTHrP/PTH1R signaling pathway.The primary chondrocytes of Igf1r-inducible knockout mice were constructed by in vitro adenovirus infection with Cre recombinase(Ad-Cre).The expression of PTHrP/PTH1R was detected byWestern blotting after treatment with different concentrations of Ca2+.High Ca2+can significantly accelerate the differentiation process of mGPC.Ca2+signaling counteracts PTHrP/PTH1R signaling by suppressing PTH1R expression independently of IGF1/IGF1R signaling and by inhibiting PTHrP expression via the IGF1R-dependent pathway to support normal progression of chondrocyte differentiation and growth plate development.The rate of differentiation of mouse growth plate chondrocytes depends on the equilibrium state of interaction between PTHrP/PTH1R and extracellular Ca2+signaling.
作者 石法亮 李龙云 程勇杰 Shi Faliang;Li Longyun;Cheng Yongjie(Qingdao West Coast New District People's Hospital,Qingdao,266400)
出处 《基因组学与应用生物学》 CAS CSCD 北大核心 2019年第10期4703-4708,共6页 Genomics and Applied Biology
基金 青岛市科学技术项目(J2005-2-56)资助
关键词 IGF1R 软骨细胞 生长板发育 PTHRP PTH1R IGF1R Chondrocytes Growth plate development PTHrP PTH1R
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