细胞外基质在骨关节炎发生、发展中的作用及临床研究价值

The role of extracellular matrix in the occurrence and development of osteoarthritis and its clinical research value

背景:细胞外基质代谢失衡影响结构支持作用、细胞间信号转导和细胞增殖、分化及迁移等细胞行为,在骨关节炎发生、发展中发挥着重要作用。目的:阐释细胞外基质在骨关节炎发生、发展中的作用,并分析其在骨关节炎诊断、治疗等方面的应用前景。方法:检索MEDLINE、PubMed、万方和中国知网数据库收录的2014-2021年发表的与细胞外基质在骨关节炎发生、发展中的作用相关文献。中文检索词:"骨关节炎、软骨、软骨细胞、细胞外基质、治疗、信号通路、生物标记物、组织工程",英文检索词:"Osteoarthritis,Cartilage,Cartilage cells,Extracellular matrix,Treatment,Signaling pathway,Biomarkers,Tissue engineering"。结果与结论:(1)细胞外基质作为关节软骨的重要组成部分,除为软骨细胞提供营养外,还形成了具有一定保护作用且适合软骨细胞生长的复杂三维结构。(2)细胞外基质是软骨细胞与外界环境进行信息交换的场所,感受外界刺激并作出响应,进而调节软骨细胞增殖及凋亡等行为。(3)细胞外基质中还含有大量生物标记物因子,如Ⅱ型胶原降解的标记物Ⅱ型胶原羧基端端肽、Ⅱ型胶原α1和基质金属蛋白酶等,可作为包括骨关节炎在内的多种疾病的辅助诊断及鉴别诊断。(4)基于细胞外基质的组织工程策略目前已被广泛应用于多种组织再生的研究中,如单纯的脱细胞细胞外基质支架、负载干细胞或特定药物诱导细胞行为的细胞外基质支架、仿生天然细胞外基质结构和生物学功能的复合支架等,在软骨组织工程中占据着重要地位。(5)软骨细胞外基质在骨关节炎发生、发展、诊断及治疗等方面均有着广阔的研究和应用前景,但目前软骨细胞外基质的变化与骨关节炎发生、发展相关的研究较少,而临床应用研究更少。(6)如何在骨关节炎的诊断、预防和治疗中充分利用细胞外基质的理化性质并充分发挥各组分的功能,从而实现更准确的骨关节炎分期诊断,以提供更优的治疗手段,未来还需更深入的研究验证。

BACKGROUND:The imbalance of extracellular matrix metabolism affects the structure support and intercellular signal transduction,cell proliferation,differentiation and migration,which plays an important role in the occurrence and development of osteoarthritis.OBJECTIVE:To elucidate the role of extracellular matrix in the occurrence and development of osteoarthritis,and review its application prospects in the diagnosis and treatment of osteoarthritis.METHODS:WanFang,CNKI,PubMed and MEDLINE databases were retrieved respectively with the keywords of"osteoarthritis,cartilage,cartilage cells,extracellular matrix,treatment,signaling pathway,biomarkers,tissue engineering"in Chinese and English,respectively.Articles regarding the role of extracellular matrix in the occurrence and development of osteoarthritis published from 2014 to 2021 were included.RESULTS AND CONCLUSION:(1)As an important component of articular cartilage,the extracellular matrix provides nutrients to chondrocytes,and forms a complex three-dimensional structure with protective effect and suitable for the growth of chondrocytes.(2)The extracellular matrix is a place for chondrocytes to exchange information with the environment,to feel and respond to external stimuli,and thereby to regulate the proliferation,apoptosis and other behaviors.(3)Extracellular matrix also contains a large number of biomarkers,such as type II collagen carboxy-terminal peptide,type II collagenα1 and matrix metalloproteinase,which can be used for auxiliary diagnosis and differential diagnosis of a variety of diseases including osteoarthritis.(4)In terms of treatment,tissue engineering strategies based on the extracellular matrix have been widely used in a variety of tissue regeneration studies and play an important role in cartilage tissue engineering,such as simple acellular extracellular matrix scaffolds,extracellular matrix scaffolds loaded with stem cells or specific drugs to induce cell behaviors,and composite scaffolds with bionic natural extracellular matrix structure and biological functions.(5)In conclusion,cartilage extracellular matrix has broad research and application prospects in the occurrence,development,diagnosis and treatment of osteoarthritis.However,there are few studies related to cartilage extracellular matrix changes and the occurrence and development of osteoarthritis,and there are much fewer studies related to clinical application.However,how to make full use of the physicochemical properties of extracellular matrix and give full play to the functions of each component in the diagnosis,prevention and treatment of diseases still needs more in-depth research,in order to achieve more accurate diagnosis and staging of osteoarthritis,and provide better treatment means.