Osteoimmunology in skeletal cell biology and disease.
Osteoimmunology in skeletal cell biology and disease.
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骨骼细胞生物学和疾病中的骨免疫学。
DOI：
10.1080/08916930701694808
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发表时间：
2008
期刊：
影响因子：
3.5
通讯作者：
McHugh,KevinP
中科院分区：
文献类型：
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作者：
McHugh,KevinP
过去十年的科学进步使骨骼生物学领域发生了革命性的变化。骨骼细胞生物学的遗传和基因组方法导致了一些意想不到的细胞和细胞因子相互作用的鉴定革命。免疫细胞和介质在骨骼生物学中作为主要调节因子的普遍存在就是这样一个启示。术语“骨免疫学”最初是由Arron和Choi提出的，用来描述这一新的生物学学科，该学科旨在定义免疫细胞与骨骼细胞的作用和相互作用，并确定共享的途径和信号分子。在这里，我们介绍骨免疫细胞相互作用的综述，考虑免疫细胞和骨细胞之间共享的细胞内信号分子、细胞表面分子和细胞因子。这些骨免疫相互作用的讨论，在代谢骨转换，炎症和疾病的光。我们还希望拓宽骨免疫学的范围，使其更包括先天免疫相互作用、炎症的解决以及骨代谢和免疫系统之间的信号传导的新介质。在第一篇综述中，Wu、Humphrey和Nakamura介绍了骨吸收破骨细胞作为一种先天免疫细胞，其分化和功能依赖于细胞因子受体激活因子NFkB （RANKL）和巨噬细胞集落刺激因子。最近，免疫受体酪氨酸基激活基序（ITAM）信号受体DAP12和FcRg被证明直接影响破骨细胞的形成、功能和调节骨量。在破骨细胞形成过程中，ITAM信号作为共刺激因子的需求与ITAM受体在其他肿瘤坏死因子家族受体介导的免疫细胞功能中的共刺激需求相似。讨论了人类和小鼠ITAM受体通路突变的研究，揭示了ITAM信号传导对骨骼生物学的微环境和局部影响。toll样受体（TLRs）识别病原体相关分子模式（PAMPs）并介导对它们的先天免疫反应。Bar-Shavit博士描述了这些先天免疫受体在骨细胞生物学中的作用，指出tlr与RANK信号通路共享。关于破骨细胞形成中的PAMP效应和TLR信号的研究常常与抗和促破骨功能相矛盾。Bar-Shavit博士阐明了TLR对破骨细胞分化的相反作用，并强调了破骨细胞前体的RANKL启动对促破骨TLR信号传导的要求。Bar-Shavit博士还阐述了PAMP通过破骨细胞和成骨细胞之间的串音调节骨代谢，并提出了PAMP通过tlr调节骨吸收的模型。
Scientific advances within the last decade have revolutionized the field of skeletal biology. Genetic and genomic approaches to skeletal cell biology led the revolution with the identification of some unexpected cellular and cytokine interactions. The prevalence of immune cells and mediators as major regulatory factors in skeletal biology has been one such revelation. The term “Osteoimmunology” was first suggested by Arron and Choi to describe this new discipline of Biology which seeks to define the roles and interactions of immune cells with skeletal cells and to identify shared pathways and signaling molecules. Here we present reviews on osteoimmunological cellular interactions, considering shared intracellular signaling molecules, cell surface molecules, and cytokines between immune and bone cells. These osteoimmunological interactions are discussed in light of metabolic bone turnover, in inflammation and in disease. We also wish to perhaps broaden the scope of osteoimmunology to be more inclusive of innate immune interactions, resolution of inflammation, and novel mediators of signaling between bone metabolism and the immune system. In the first review, Wu, Humphrey, and Nakamura introduce the bone-resorbing osteoclast as an innate immune cell, which is dependent on the cytokines receptor-activator NFkB (RANKL) and macrophage colony stimulating factor for differentiation and function. Recently, the immunoreceptor tyrosinebased activation motif (ITAM) signaling receptors DAP12 and FcRg have been shown to directly impact osteoclast formation, function, and to modulate bone mass. The requirement for ITAM signaling as a costimulatory factor in osteoclast formation parallels that of co-stimulation by ITAM receptors in other TNF family receptor-mediated immune cell functions in other immune cell types. Studies of human and mouse mutations in ITAM receptor pathways are discussed, revealing micro-environmental and focal influences of ITAM signaling on skeletal biology.Toll-like receptors (TLRs) recognize pathogenassociated molecular patterns (PAMPs) and mediate the innate immune responses to them. Dr Bar-Shavit describes the role of these innate immune receptors in bone cell biology, noting the shared signaling pathways for TLRs with RANK signaling. Studies of PAMP effects and TLR signaling in osteoclast formation have often been contradictory with antiand pro-osteoclastic functions reported. Dr Bar-Shavit clarifies the opposing effects of TLRs on osteoclast differentiation, and highlights the requirement for RANKL priming of osteoclast precursors for pro-osteoclastic TLR signaling. Dr Bar-Shavit also addresses PAMP regulation of bone metabolism by cross-talk between osteoclasts and osteoblasts, and presents a model of modulation of bone resorption by PAMPs through TLRs.