University of Ljubljana, Faculty of Pharmacy, Department of Clinical Biochemistry, Ljubljana, Slovenia.
Biochem Med (Zagreb). 2013;23(1):43-63. doi: 10.11613/bm.2013.007.
Bone and immune system are functionally interconnected. Immune and bone cells derive from same progenitors in the bone marrow, they share a common microenvironment and are being influenced by similar mediators. The evidence on increased bone resorption associated with inappropriate activation of T cells such as during inflammation, is well established. However, the molecular mechanisms beyond this clinical observation have begun to be intensively studied with the advancement of osteoimmunology. Now days, we have firm evidence on the influence of numerous proinflammatory cytokines on bone cells, with the majority of data focused on osteoclasts, the bone resorbing cells. It has been shown that some proinflammatory cytokines could possess osteoclastogenic and/or anti-osteoclastogenic properties and can target osteoclasts directly or via receptor activator of nuclear factor kappaB (RANK)/RANK ligand(RANKL)/osteoprotegerin (OPG) system. Several studies have reported opposing data regarding (anti)osteoclastogenic properties of these cytokines. Therefore, the first part of this review is summarizing current evidence on the influence of pro-inflammatory cytokines on osteoclasts and thus on bone resorption. In the second part, the evidence on the role of pro-inflammatory cytokines in osteoporosis and osteoarthritis is reviewed to show that unravelling the mechanisms beyond such complex bone diseases, is almost impossible without considering skeletal and immune systems as an indivisible integrated system.
骨骼和免疫系统在功能上是相互关联的。免疫细胞和骨细胞都来源于骨髓中的同一祖细胞，它们共享一个共同的微环境，并受到相似介质的影响。在炎症等情况下，T 细胞异常激活导致骨吸收增加的证据已经得到充分证实。然而，随着骨免疫学的发展，超越这一临床观察的分子机制已经开始得到深入研究。如今，我们有确凿的证据表明，许多促炎细胞因子会影响骨细胞，其中大部分数据集中在破骨细胞上，即骨吸收细胞。已经表明，一些促炎细胞因子可能具有破骨细胞生成和/或抗破骨细胞生成特性，并且可以直接或通过核因子 kappaB（NF-κB）受体激活剂（RANK）/RANK 配体（RANKL）/骨保护素（OPG）系统靶向破骨细胞。有几项研究报告了这些细胞因子在（抗）破骨细胞生成特性方面相互矛盾的数据。因此，这篇综述的第一部分总结了促炎细胞因子对破骨细胞进而对骨吸收的影响的现有证据。在第二部分，回顾了促炎细胞因子在骨质疏松症和骨关节炎中的作用的证据，以表明，如果不将骨骼和免疫系统视为一个不可分割的整体系统，那么揭示这些复杂骨骼疾病背后的机制几乎是不可能的。
