Osteoclasts: What do they do and how do they do it?
Osteoclasts: What do they do and how do they do it?
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DOI：
10.2353/ajpath.2007.060834
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发表时间：
2007-02-01
影响因子：
6
通讯作者：
Teitelbaum, Steven L.
中科院分区：
文献类型：
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作者：
Teitelbaum, Steven L.
随着美国人年龄的增长，骨质疏松症等退行性骨骼疾病变得越来越普遍。不管原因如何，骨质疏松症反映了破骨细胞活性的相对增强。因此，这种独特的骨吸收细胞是一个突出的治疗靶点。一些关键的观察提供了对前体细胞转化为破骨细胞表型的机制以及成熟细胞如何降解骨的见解。破骨细胞是单核细胞/巨噬细胞家族的成员，在两种关键细胞因子（即RANK配体和M-CSF）的保护下分化。肿瘤坏死因子（TNF）-α也促进破骨细胞生成，特别是在炎性骨质溶解状态下，如类风湿性关节炎。一旦分化，破骨细胞通过α v β 3整联蛋白与骨表面形成密切的关系，α v β 3整联蛋白传递基质衍生的细胞因子组织信号。这些整合素传递的信号包括相关蛋白质c-src、syk、Vav 3和Rho GTP酶的激活。有组织的细胞骨架在细胞质膜和骨表面之间产生一个孤立的微环境，其中基质矿物质被酸性环境动员，有机基质被溶酶体蛋白酶组织蛋白酶K降解。本文综述了这些和其他介导破骨细胞分化或功能的分子，从而作为候选的抗骨质疏松症治疗靶点。
As Americans five longer, degenerative skeletal diseases, such as osteoporosis, become increasingly prevalent. Regardless of cause, osteoporosis reflects a relative enhancement of osteoclast activity. Thus, this unique bone resorptive cell is a prominent therapeutic target. A number of key observations provide insights into the mechanisms by which precursors commit to the osteoclast phenotype and how the mature cell degrades bone. The osteoclast is a member of the monocyte/macrophage family that differentiates under the aegis of two critical cytokines, namely RANK ligand and M-CSF. Tumor necrosis factor (TNF)-alpha also promotes osteoclastogenesis, particularly in states of inflammatory osteolysis such as that attending rheumatoid arthritis. Once differentiated, the osteoclast forms an intimate relationship with the bone surface via the av beta 3 integrin, which transmits matrix-derived, cytoskeleton-organizing, signals. These integrin-transmitted signals include activation of the associated proteins, c-src, syk, Vav3, and Rho GTPases. The organized cytoskeleton generates an isolated microenvironment between the cell's plasma membrane and the bone surface in which matrix mineral is mobilized by the acidic milieu and organic matrix is degraded by the lysosomal protease, cathepsin K. This review focuses on these and other molecules that mediate osteoclast differentiation or function and thus serve as candidate anti-osteoporosis therapeutic targets.