摘要
遗传性多发性骨软骨瘤(hereditary multiple exostoses,HME)是以常染色体显性遗传为特征的良性骨肿瘤,可导致青少年骨发育畸形,严重影响机体美观及运动功能。目前,HME尚无诊疗指南,其主要治疗方式为手术治疗,切除肿瘤并矫正畸形。但骨软骨瘤具有多发性,难以全部切除。因此,越来越多的学者正在探索保守治疗的方法。但当前对HME发病机制的认识有限,临床尚无安全、有效的药物。关于HME发病机制的相关假说多基于遗传基因突变,HME患者可能发生了因基因杂合性缺失等二次突变而导致的EXT抑癌基因突变及功能丧失,最终诱导生长板中软骨增殖及分化异常。EXT基因表达异常引起硫酸乙酰肝素(heparan sulphate,HS)水平的降低,导致多条调控生长板软骨细胞发育及分化的分子信号通路异常,共同参与HME的发生、发展全过程。本文综述了近年来关于HME发病机制的相关研究,以期更好地理解HME的病理过程,为HME的诊疗提供理论依据,同时也为HME靶点药物的研发提供思路。
Hereditary multiple exostoses(HME)are benign bone tumors characterized by autosomal dominant inheritance,which can cause skeletal malformation in adolescents,seriously affecting the body's aesthetic and motor functions.Currently,there are no guidelines for diagnosing and treating HME,and the main treatment is surgical treatment to remove the tumor and correct the deformity.However,osteochondroma is multiple and difficult to be completely resected.Therefore,more and more scholars are exploring the method of conservative treatment.However,the current understanding of the pathogenesis of HME is limited,and there are no safe and effective drugs in the clinic.Most hypotheses regarding the pathogenesis of HME are based on genetic mutations.Patients with HME may have EXT tumor suppressor gene mutations and function loss caused by secondary mutations such as loss of gene heterozygosity,which ultimately induce abnormal proliferation and differentiation of cartilage in growth plates.Abnormal EXT gene expression causes a decrease in the level of heparan sulphate(HS),leading to abnormalities in multiple molecular pathways that regulate the development and differentiation of growth plate chondrocytes,which together participate in the entire process of HME development and progression.This paper reviews the relevant studies on the pathogenesis of HME in recent years,in order to better understand the pathological process of HME,provide a theoretical basis for the diagnosis and treatment of HME,and also provide ideas for the development of drugs targeting HME.
作者
韦帧翟
廖世杰
黄乾
李波香
丁晓飞
Wei Zhendi;Liao Shijie;Huang Qian;Li Boxiang;Ding Xiaofei
出处
《中华骨科杂志》
CAS
CSCD
北大核心
2023年第10期670-676,共7页
Chinese Journal of Orthopaedics
基金
国家自然科学基金(82060396)。
关键词
骨软骨瘤病
癌基因
突变
硫酸乙酰肝素
Osteochondromatosis
Oncogenes
Mutation
Heparitin Sulfate
