Bone, Joint, Cancer Unit, St Vincent's Institute, Fitzroy, Victoria, Australia.
Immunol Rev. 2010 Jan;233(1):301-12. doi: 10.1111/j.0105-2896.2009.00857.x.
The past decade has observed an explosion of new information regarding the impact of inflammation on bone. In rheumatic diseases, several factors that act as both immune modulators and regulators of bone homeostasis have been shown to mediate an imbalance in bone resorption and bone formation resulting in joint degeneration. In rheumatoid arthritis (RA), focal bone loss is due to excess bone resorption by osteoclasts. Resorption is mediated in part by increased local expression of the cytokine receptor activator of nuclear factor-kappaB ligand (RANKL) compared with expression of its decoy receptor osteoprotegerin (OPG). Bone formation by osteoblasts is also impaired at erosion sites in RA, and inhibitors of the canonical Wingless (Wnt) signaling pathway, including DKK1, have been implicated in the suppression of normal osteoblast function at these sites. Inhibition of DKK1 in an animal model of RA attenuated bone erosion by increasing OPG expression as well as promoting bone formation. In contrast to RA, inflammation in the spondyloarthropathies often results in excess periosteal bone formation, highlighting that the net impact of inflammation on bone is specific to the site at which inflammation occurs, and the cell types, cytokines, and factors present within the local bone microenvironment. This fertile area of research bears watching for the identification of novel targets for the prevention of abnormal bone remodeling in inflammatory diseases.
过去十年中，有关炎症对骨骼影响的新信息呈爆炸式增长。在风湿性疾病中，已发现几种同时作为免疫调节剂和骨稳态调节剂的因素可介导骨吸收和骨形成之间的失衡，从而导致关节退化。在类风湿关节炎（RA）中，局部骨丢失是由于破骨细胞过度吸收骨所致。部分原因是与骨保护素（OPG）的表达相比，局部细胞因子核因子-κB 配体（RANKL）的细胞因子受体激活剂的表达增加介导了吸收。RA 侵蚀部位的成骨细胞的骨形成也受到损害，经典 Wingless（Wnt）信号通路的抑制剂，包括 DKK1，被认为在这些部位抑制正常成骨细胞功能。在 RA 的动物模型中，抑制 DKK1 通过增加 OPG 表达以及促进骨形成来减轻骨侵蚀。与 RA 相反，脊柱关节病中的炎症通常导致骨膜过度形成，这突出表明炎症对骨骼的净影响特定于炎症发生的部位以及局部骨微环境中存在的细胞类型、细胞因子和因素。这个充满活力的研究领域值得关注，以期确定预防炎症性疾病中异常骨重塑的新靶点。
