破骨细胞融合蛋白的研究进展

doi:10.3877/cma.j.issn.1674-1366.2020.04.002

破骨细胞是具有骨吸收能力的多核巨细胞。在破骨细胞分化过程中，细胞因子刺激破骨细胞前体细胞表达融合蛋白，如树突状细胞特异性跨膜蛋白（DC-STAMP）、破骨细胞多次跨膜蛋白（OC-STAMP），为破骨细胞融合奠定基础。在疾病状态下，细胞因子的分泌异常，导致破骨细胞融合蛋白表达增加。这促进破骨细胞前体细胞融合形成骨吸收能力更强的破骨细胞。破骨细胞融合蛋白的异常表达是破骨细胞造成病理性骨破坏的前提。阐明破骨细胞融合蛋白的作用机制，对于干预骨破坏性疾病具有一定意义。基于此，本文通过论述破骨细胞融合蛋白的研究现状，为进一步研究破骨细胞造成的骨破坏性疾病提供参考。

关键词: 破骨细胞, 细胞融合, 膜蛋白

Osteoclasts are multinucleated giant cells with bone resorption capacity. During osteoclast differentiation, cytokines stimulate the expression of fusion proteins on cell surface of osteoclast precursors, such as dendritic cell-specific transmembrane protein (DC-STAMP) , osteoclast-stimulatory transmembrane protein (OC-STAMP) , etc., which lay foundation for osteoclast fusion. Under pathological conditions, abnormal secretion of cytokines leads to increased expression of osteoclast fusion proteins, which promotes the fusion of osteoclast precursors to form osteoclasts with stronger bone resorption capacity. Aberrant expression of osteoclast fusion proteins is a prerequisite for pathological bone destruction caused by osteoclasts. Elucidation of the mechanisms underlying the roles of fusion proteins in osteoclasts is of great significance for the intervention of bone destructive diseases. In this article, we expound the research status of osteoclast fusion proteins to provide references for the further study of osteoclast-related bone destructive diseases.

Key words: Osteoclasts, Cell fusion, Membrane proteins

图1 破骨细胞前体细胞分化及融合过程（1）单核-巨噬细胞在巨噬细胞集落刺激因子（M-CSF）、核因子κB受体激活子配体（RANKL）刺激下增殖、分化成破骨细胞前体细胞，同时表达破骨细胞融合蛋白。（2）破骨细胞融合早期，单核及少量核破骨细胞前体细胞以"宽接触面"的形式发生融合。破骨细胞前体细胞的融合起始于细胞膜的极化突起以及伪足。E-钙粘蛋白、破骨细胞多次跨膜蛋白（OC-STAMP）、白细胞分化抗原9（CD9）、CD47及其受体信号调节蛋白α等在破骨细胞前体细胞融合早期表达。E-钙粘蛋白主要分布于细胞膜突起以及板状伪足；通过形成同型二聚体，促进破骨细胞前体细胞的接触与融合。CD47表达于破骨细胞前体细胞融合接触面，通过结合受体信号调节蛋白α，促进破骨细胞前体细胞的接触；随着破骨细胞的融合，细胞膜表面CD47减少。RANKL刺激后，CD9位于细胞膜表面的微结构域脂筏上，同时分布于前体细胞的细胞突起。OC-STAMP、囊泡型ATP酶V0结构域d2亚单位（ATP6v0d2）在破骨细胞融合早期表达，OC-STAMP随着破骨细胞前体细胞融合减少，两者具体作用形式有待研究。（3）破骨细胞融合晚期，多核破骨细胞前体主要以"吞噬杯"的形式发生融合。在多核破骨细胞前体细胞融合接触面，树突状细胞特异性跨膜蛋白（DC-STAMP）与其未知配体结合、合胞素1（Syn-1）与受体谷氨酰胺转运载体（ASCT2）结合，促进其膜接触及融合。（4）破骨细胞前体细胞相互融合后，进一步分化成为具有功能的破骨细胞，表达组织蛋白酶K、耐酒石酸酸性磷酸酶等破骨细胞标记物

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Research advances of fusion proteins in osteoclasts

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Research advances of fusion proteins in osteoclasts