痛风致骨破坏机制的研究与进展

Research progress in gout-induced bone destruction mechanism

背景:慢性痛风患者体内尿酸钠盐沉积在骨关节、滑膜周围,侵蚀、破坏骨质,导致痛风性关节炎和畸形等严重并发症。研究尿酸钠晶体侵蚀和破坏骨质的机制,有助于临床早期干预痛风性疾病,预防和延缓骨破坏引起的并发症。目的:通过临床影像学研究和实验性基础研究探讨痛风晶体对骨质的破坏作用,综述目前痛风导致骨破坏现象和机制研究进展和和发展前景,指导临床早期干预痛风性骨破坏,为研究骨破坏作用指引方向。方法:通过计算机检索万方、PubMed等数据库,中文检索词为“痛风,骨破坏,骨侵蚀”;英文检索词为“tophi,gout,RANKL,bone destruction,bone erosion”,通过纳入与排除标准,最终选择64篇文献进行归纳总结。结果与结论:临床研究(影像、组织病理学)的特异性表现一定程度上阐述了痛风的溶骨过程,在基础研究中,痛风致骨破坏机制可分以下5方面:①尿酸钠晶体对骨破坏有重要作用,直接影响骨细胞、软骨细胞、成骨细胞和促骨吸收因子促进骨破坏;②核因子κB受体活化因子配体(RNAKL)等促吸收因子参与骨破坏;③T细胞介导的细胞免疫在骨破坏中起桥梁作用,激活的T细胞诱导破骨细胞分化;④单核/巨噬细胞不但是破骨样细胞的前体,而且可以诱导核因子κB受体活化因子配体等促吸收因子表达;⑤中性粒细胞影响骨细胞排列形态,中性粒细胞外诱捕网通过促进破骨细胞分化促进溶骨。

BACKGROUND:In chronic gout patients,sodium urate is deposited in bone joints and around synovial membranes,eroding and destroying bone,leading to serious complications such as gouty arthritis and deformity.Research on the mechanisms by which sodium urate crystals erode and destroy bone can help early clinical intervention in gouty diseases and prevent and delay the complications caused by bone destruction.OBJECTIVE:To explore the destructive effects of gout crystals on bone through clinical imaging studies and experimental basic research,review the current progress and development prospects of research on the phenomenon and mechanism of bone destruction caused by gout,guide the clinical early intervention of gouty bone destruction,and guide the direction of research on the role of bone destruction.METHODS:The Chinese search terms were“gout,bone destruction,bone erosion”and the English search terms were“tophi,gout,RANKL,bone destruction,bone erosion,”which were used in the computer search of WanFang and PubMed databases.Finally,64 articles were selected for review according to the inclusion and exclusion criteria.RESULTS AND CONCLUSION:The specific manifestations of clinical studies(imaging,histopathology)to some extent elaborate the osteolytic process of gout,and in basic studies,the mechanism of gout-causing bone destruction can be divided into the five aspects:(1)Sodium acid crystals have an important role in bone destruction,directly affecting osteocytes,chondrocytes,osteoblasts and proresorptive factors that promote bone destruction;(2)Receptor activator of nuclear factor-κB ligand and other proresorptive factors are involved in bone destruction;(3)T cell-mediated cellular immunity functions as a bridge in bone destruction,and activated T cells induce osteoclast differentiation;(4)Monocytes/macrophages are not only precursors of osteoclast-like cells,but also induce the expression of proresorptive factors such as Receptor activator of nuclear factor-κB ligand;(5)Neutrophils affect the morphology of osteoclast arrangement,and neutrophil extracellular trap networks promote osteolysis by promoting osteoclast differentiation.