黄韧带骨化机制与骨质疏松症治疗策略  

Mechanism of ossification of the ligamentum flavum and treatment strategy of osteoporosis

作　　者：常亚南 舒丽 张驰 CHANG Yanan;SHU Li;ZHANG Chi(Central Laboratory,Peking University International Hospital,Beijing l02206;Department of Orthopedics,Peking University International Hospital,Beijing l02206;Biomedical Engineering Department,Peking University,Beijing l02206,China)

机构地区：[1]北京大学国际医院中心实验室,北京102206 [2]北京大学国际医院骨科,北京102206 [3]北京大学跨学部生物医学工程系,北京102206

出　　处：《中国骨质疏松杂志》2021年第8期1238-1244,共7页Chinese Journal of Osteoporosis

基　　金：北京市科技重大专项基金(Z181100001818006)。

摘　　要：骨质疏松症是最常见的代谢性骨病,因成骨细胞与破骨细胞功能失衡造成。目前常见的骨质疏松症药物旨在抑制骨吸收。为了更有效地治疗骨质疏松症,刺激新骨形成将是重要策略。成骨细胞特异转录因子Osterix(Osx)是骨形成及成骨细胞分化必需的转录因子,被认为是骨分子开关。全基因组关联分析研究已经证实Osx与骨质疏松表型相关,但仍需进一步研究Osx的作用机制,包括探索Osx上游调节因子。骨质疏松症迫切需要促骨形成新药,Osx是理想的新靶点。而临床上的另外一种疾病为寻找Osx上游因子提供了很好的参考,那就是黄韧带骨化(ossification of the ligamentum flavum,OLF)。黄韧带骨化是脊柱韧带病理性异位骨化性疾病,在骨外组织黄韧带里刺激了新骨的形成,其致病机制尚不明确。本文结合近年来有关黄韧带骨化的一些机制研究进行综述,包括力学因素、遗传因素、内分泌以及微量元素、Notch信号通路、miRNA及炎症因子等。最新发现的一些参与黄韧带骨化的相关因子能够刺激Osx基因的表达,希望通过对黄韧带骨化致病机制的研究,为寻找Osx上游调节因子进而研发促骨形成新药治疗骨质疏松症提供新的思路。Osteoporosis is the most common metabolic bone disease,which is caused by the imbalance of osteoblast and osteoclast function.Current osteoporosis drugs aim to inhibit bone resorption.In order to treat osteoporosis more effectively,stimulating newbone formation will be an important strategy.Osteoblast specific transcription factor Osterix(Osx)is an essential transcription factor for bone formation and osteoblast differentiation,and is considered as a bone molecular switch.Genome wide association analysis has confirmed that Osx is associated with osteoporosis phenotype.However,the mechanism of Osx deserves further investigation,including exploring the upstream regulatory factors of Osx.Osteoporosis urgently needs newdrugs to promote bone formation,and Osx is an ideal newtarget.The ossification of the ligamentum flavum(OLF)is another clinical disease that provides a good reference for the search for the upstream factors of Osx.Ossification of ligamentum flavum is a pathological heterotopic ossification disease of spinal ligament.It stimulates the formation of newbone in the ligamentum flavum,and its pathogenesis is still unclear.In this review,we reviewed the mechanism of ligamentum flavum ossification in recent years,including mechanical factors,genetic factors,endocrine and trace elements,Notch signaling pathway,miRNA and inflammatory factors,and so on.Some newly discovered factors involved in ligamentum flavum ossification can stimulate the expression of Osx gene.The study on the pathogenesis of ossification of ligamentum flavum can provide a newidea for searching the upstream regulatory factors of Osx and developing newdrugs for promoting bone formation in the treatment of osteoporosis.

关 键 词：骨质疏松症 致病机制 成骨细胞特异转录因子Osx 黄韧带骨化 

分 类 号：R681[医药卫生—骨科学]