胸椎黄韧带骨化相关分子信号通路的研究进展

Research progress of molecular signaling pathways in thoracic ossification of ligamentum flavum

胸椎黄韧带骨化症(thoracic ossification of ligament flavum,TOLF)系脊柱韧带异位骨化性疾病之一,是导致胸椎管狭窄的主要原因,在中国、日本等东亚国家发病率较高。由于TOLF的病理本质为软骨内成骨,所以保守治疗无法根治,手术干预是目前惟一有效的治疗方法。TOLF患者年龄普遍较大,且起病隐匿,症状、体征各异,定位诊断困难,手术难度较大,术后并发症发生率较高,因此研究TOLF的成骨分化机制以找到早期诊断和预防的手段尤为重要。目前,已发现多种因素与TOLF的成骨分化有关,如遗传、机械刺激、分子生物学因素、代谢及微量元素异常等,而分子信号通路对于调节细胞的增殖和定向分化起到至关重要的作用。因此,本综述系统性总结参与调控黄韧带骨化过程的相关信号通路,包括骨形态发生蛋白(bone morphogenetic protein,BMP)信号通路、丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)信号通路、Wnt信号通路、Notch信号通路、STAT3信号通路以及其他信号通路和因子,同时分析这些信号通路在黄韧带细胞成骨分化中发挥促进或者抑制作用,可为进一步探究TOLF的分子生物学机制提供依据,也为更深入探索有效的治疗靶点和预防方式提供可能的方向。

Thoracic ossification of ligament flavum(TOLF)is a chronic progressive disease presenting the heterotopic ossification of the ligamentum flavum of the thoracic spine,which leads to a series of symptoms and signs of thoracic spinal cord,nerveor vascular compression,with a high incidence in East Asian countries such as China and Japan.The pathology of TOLF is endochondral ossification in nature and surgical intervention is currently the only effective treatment due to conservative treatment does not work.The older age,the insidious onset,the various clinical manifestations of TOLF patients make the localization diagnosis and surgery management difficult and even bring about the high incidence of postoperative complications.Therefore,it is particularly important to study the mechanism of osteogenic differentiation of TOLF to find a way of early diagnosis and prevention.A variety of factors related to osteogenic differentiation of TOLF have been found,such as genetics,mechanical stimuli,molecular biological factors,metabolic and trace element abnormalities and so on.Moreover,molecular signaling pathways play a crucial role in regulating cell proliferation and directed differentiation.Therefore,this article reviews the confirmed relevant signaling pathways in the process of ligamentum flavum ossification,including bone morphogenetic protein(BMP)signaling pathway,mitogen-activated protein kinase(MAPK)signaling pathway,Wnt signaling pathway,Notch signaling pathway,STAT3 signaling pathway and other signaling pathways and factors,and also summarizes the promotion and inhibition of these signaling pathways in the osteogenic differentiation of ligamentum flavum cells,aiming at establishing a basis for the further research of the molecular biological mechanism of TOLF,and providing a possible direction for exploration of effective preventive and therapeutic targets.