TLR4/NF-κB信号通路在激素性股骨头坏死的作用△

Role of TLR4 / NF-κB signaling pathway in steroid-induced osteonecrosis of the femoral head

摘要:

激素性股骨头坏死（steroid-induced osteonecrosis of the femoral head, SONFH）是由于糖皮质激素的大量使用最终造成股骨头坏死的一种代谢性疾病，而 SONFH 的发病机制迄今仍未完全明确，存在各种假说。研究表明，巨噬细胞参与的炎症反应可能是激素性股骨头坏死发生发展的重要促发因素之一。Toll 样受体 4（toll like receptor 4, TLR4）/核转录因子-κB（(nuclear factor kappa-B, NF-κB） 炎症信号通路能被短期内过量或长期使用的糖皮质激素激活，致 NF-κB 活化，使其原有结构发生改变，继而转入细胞核启动基因表达释放出大量炎性介质，如肿瘤坏死因子-α （tumor necrosis factorα, TNF-α）、白细胞介素-1β （interleukin-1beta, IL-1β）、白细胞介素-6（interleukin-6, IL-6）等，使破骨细胞分化增强，骨吸收增加，同时抑制成骨细胞分化和骨形成，诱发其凋亡，对骨的结构造成影响，破坏骨稳态，最终引发股骨头塌陷、坏死。本文对 TLR4/NF-κB 信号通路参与 SONFH 进展的可能作用机制进行综述，为 SONFH 的预防和治疗提供新思路。

Abstract:

Steroid -induced osteonecrosis of the femoral head (SONFH) is a metabolic disease caused by the extensive use of glucocorticoid. The pathogenesis of SONFH is still not completely clear, yet there are various hypotheses. Studies have shown that the inflammatory reaction of macrophages may be one of the important factors to impel the development of SONFH. The TLR4/NF-κB inflammatory signaling pathway can be activated by excessive glucocorticoid in the short-term or long term, resulting in the activation of NF-κB, which changes the original structural state of NF-κB, and then transmits to the nuclear promoter gene expression to release a large number of inflammatory mediators, such as TNF-α, Il-1β, IL-6, etc. They inhibits osteoblast differentiation and bone formation, induces osteoblast apoptosis, at the same time, enhances osteoclast differentiation, increases bone resorption and destroys bone homeostasis, eventually leading to collapse and necrosis of femoral head. This article reviews the possible mechanism of TLR4/NF-ΚB signaling pathway in the progression of SONFH, providing a reference for the prevention and treatment of SONFH.