破骨细胞分化因子及其信号转导通路

摘要

破骨细胞负责骨吸收，来源于骨髓单核-巨噬细胞系，其分化需巨噬细胞发育必需集落刺激因子的参与。破骨细胞形成和分化过程中所必须的细胞间信号转导则由骨保护蛋189白（OPG）以及核因子-κB（NF-κB）受体活化因子（RANK）及其配体（RANKL）系统介导。RANKL-RANK-OPG信号转导通路在多种因子共同参与下，通过NF-κB、促丝裂原激活蛋白激酶和磷脂酰肌醇-3-激酶-蛋白激酶B等信号转导通路实现信号转导。肿瘤坏死因子-α可刺激成骨细胞产生粒细胞-巨噬细胞集落刺激因子和白细胞介素（IL）-6等因子，诱使破骨细胞前体分化为破骨细胞。一氧化氮和雌激素影响破骨细胞前体的分化。整联蛋白-αvβ3在破骨细胞诱导酪氨酸磷酸化与富含脯氨酸的酪氨酸激酶2及非受体依赖型蛋白酪氨酸激酶Src家族中的衔接蛋白P130 Crk相关的底物蛋白激活中至关重要，使骨产生吸收作用。在破骨细胞及其前体中，转化生长因子-β受体、类固醇家庭受体、G-蛋白偶联受体、IL-1和非酪氨酸激酶细胞因子等对于破骨细胞功能的影响十分重要。%Osteoclastsareresponsibleforboneresorptionandcanbederivedfromthemononuclearmacrophagesystemin the bone marrow;hence, a method should be developed to differentiate macrophage colony-stimulating factor. Signal transductioninosteoclastformationandcelldifferentiationaremediatedbyosteoprotegerin(OPG)andnuclearfactorkappaB(NF-κB),particularlyitsreceptor-activatingfactor(RANK)andligand(RANKL)system.TheRANKL-RANK-OPGsignaltransductionpathwayisaffectedbyseveralfactors,includingthesignaltransductionpathwayofNF-κB,mitogen-activatedproteinkinase,andphosphatidylinositol-3-kinaseprotein.Tumornecrosisfactor-αcanstimulateosteoblaststoproducegranulocyte–macrophage colony-stimulating factor and interleukin(IL)-6 factor, thus inducing osteoclast precursors to differentiate into osteoclasts. Nitric oxide and estrogen may affect osteoclast differentiation precursors. The tyrosine kinase ofintegrinαvβ3 in osteoclast-induced tyrosine phosphorylation and proline-rich 2 region and the non-receptor-dependent protein tyrosine kinase of the Src family of adaptor proteins and P130 Crk-related proteins are important in the activation of substrates, and thus, in bone absorption. In osteoclasts and their precursors, the receptor family of transforming growth factor-β,steroidreceptors,G-proteincoupledreceptors,IL-1,andnon-tyrosinekinasecellfactorareimportantforosteoclast function.