摘要
原发性骨质疏松症是以骨质减少,骨的微观结构退化为特征的,致使骨的脆性增加以及易于发生骨折的骨骼疾病。其发病机制与多种因素相关,除了传统的内分泌机制之外,一种新的骨骼免疫机制已逐渐被深入研究:通过免疫细胞T淋巴细胞和B淋巴细胞、树突状细胞等,分泌多种细胞因子,并与多种细胞因子相互作用,通过信号通路的正负反馈调控,精细调节成骨细胞和破骨细胞的分化与增殖平衡,从而影响原发性骨质疏松症的发生。与破骨形成相关的T细胞,Th17细胞通过双重机制调控骨质吸收,Th1和Th2细胞亚群分别分泌IFN-γ和IL-4,通过抑制破骨细胞前体细胞发育成成熟的破骨细胞,从而抑制骨质吸收。Treg细胞通过表达CTLA-4,促进破骨细胞前体细胞的凋亡,抑制骨质吸收。B淋巴细胞通过调控RANKL和OPG的比例参与骨质代谢。树突状细胞既可以与CD4+T细胞结合,启动经典的RANKL/RANK破骨细胞形成的信号通路,参与骨质疏松的形成;也可以作为破骨细胞前体细胞的方式,在M-CSF等炎性因子的刺激下,直接分化为破骨细胞。现就这种免疫细胞与细胞因子精细调节骨质生成与骨质吸收平衡作用机制的最新研究进展进行阐述。
Primary osteoporosis is a bone disease characterized by systemic impairment of bone mass and the microarchitecture that results in fragility fractures. The pathogenic mechanism of osteoporosis is associated with many factors. In addition to the traditional endocrine mechanism,a newmechanism of bone-immune system interaction has been further studied: A variety of cytokines are secreted by T lymphocytes,B lymphocytes,and dendritic cells,which interact with each other,and affect the differentiation and proliferation of osteoblast and osteoclast through positive and negative feedback regulation of some signal pathways,leading to the occurrence of primary osteoporosis. T cells and Th17 cells,which are involved in osteoclast formation,regulate bone resorption by double mechanism. Th1 and Th2 subgroups inhibit bone resorption by inhibition of differentiation of osteoclast precursor cells through secretion of IFN-!and IL-4,respectively. Treg cells inhibit bone resorption by the expression of CTLA-4 to stimulate the apoptosis of osteoclast precursor cells. B lymphocytes are involved in bone metabolism by regulation of the ration of RANKL and OPG. Dendritic cells are not only involved in the development of osteoporosis by binding to CD4^+T cells to initiate the classic RANKL / RANK signal pathway in osteoclasts,but also directly differentiated into osteoclasts under the stimulation of M-CSF and other cytokines. The latest research progress about the mechanism of the regulation of bone formation and bone resorption by the interaction of the immune cells and cytokines is described.
出处
《中国骨质疏松杂志》
CAS
CSCD
北大核心
2016年第7期912-917,共6页
Chinese Journal of Osteoporosis