Advances in the Regulation of Osteoclasts and Osteoclast Functions
Advances in the Regulation of Osteoclasts and Osteoclast Functions
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DOI：
10.1177/0022034513500306
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发表时间：
2013-10-01
影响因子：
7.6
通讯作者：
Boyce, B. F.
中科院分区：
文献类型：
--
作者：
Boyce, B. F.
破骨细胞来源于单核造血髓系细胞，其在骨髓中形成并被包括鞘氨醇-1磷酸的因子吸引到血流中。这些循环的前体被趋化因子和在这些位点表达的其他因子吸引到骨表面进行再吸收，在那里它们融合形成多核骨再吸收细胞。破骨细胞形成和功能的所有方面都受到巨噬细胞集落刺激因子（M-CSF）和NF-κ B配体受体激活因子（RANKL）的调节，RANKL是破骨细胞形成所必需的细胞因子，并由多种细胞类型（包括成骨细胞谱系细胞）表达。自20世纪90年代中期发现RANKL以来，小鼠遗传和分子研究已经揭示了RANKL和M-CSF激活的许多信号通路。最近的研究表明，破骨细胞及其前体细胞通过配体和受体（如ephrin和Eph、semaphorins和plexins）的直接细胞-细胞接触以及通过表达断裂因子来调节免疫应答和成骨细胞的形成和功能。也有越来越多的认识，破骨细胞是免疫细胞，在免疫反应中的作用超出了介导骨破坏，可以伴随着他们。本文综述了调节破骨细胞形成和功能的分子机制及其在正常和病理状态下与其他细胞相互作用的最新进展。
Osteoclasts are derived from mononuclear hematopoietic myeloid lineage cells, which are formed in the bone marrow and are attracted to the bloodstream by factors, including sphingsine-1 phosphate. These circulating precursors are attracted to bone surfaces undergoing resorption by chemokines and other factors expressed at these sites, where they fuse to form multinucleated bone-resorbing cells. All aspects of osteoclast formation and functions are regulated by macrophage-colony-stimulating factor (M-CSF) and receptor activator of NF-kappa B ligand (RANKL), cytokines essential for osteoclast formation and expressed by a variety of cell types, including osteoblast lineage cells. Since the discovery of RANKL in the mid-1990s, mouse genetic and molecular studies have revealed numerous signaling pathways activated by RANKL and M-CSF. More recent studies indicate that osteoclasts and their precursors regulate immune responses and osteoblast formation and functions by means of direct cell-cell contact through ligands and receptors, such as ephrins and Ephs, and semaphorins and plexins, and through expression of clastokines. There is also growing recognition that osteoclasts are immune cells with roles in immune responses beyond mediating the bone destruction that can accompany them. This article reviews recent advances in the understanding of the molecular mechanisms regulating osteoclast formation and functions and their interactions with other cells in normal and pathologic states.