摘要
目的总结软骨前体细胞(cartilage progenitor cells,CPCs)及微小RNA-140(microRNA-140,miR-140)在骨关节炎(osteoarthritis,OA)软骨损伤修复中的作用及应用前景。方法查阅国内外近年有关CPCs、miR-140及OA软骨损伤修复的相关研究,归纳总结后进行综述。结果 CPCs具有良好的自我增殖性、干细胞表面抗原表达特性及多向分化潜能等特点,其成软骨分化能力优于其他组织来源MSCs。CPCs与OA发生发展密切相关,但其在OA软骨损伤部位自主活化及成软骨分化能力方面并不能达到软骨完全修复的要求。miR-140具有软骨特异性,参与OA发病机制,具有抑制Notch信号通路、诱导活化CPCs并增强其增殖及成软骨分化的能力,从而促进OA软骨损伤修复的潜能。关节腔局部给药是目前治疗OA的主要方式之一,关节腔注射miR-140虽然对大鼠软骨退变具有显著抑制作用,但也存在非靶向聚集、生物利用度低及清除快等问题,基于关节软骨特性构建具有良好安全性、软骨靶向性且能高效递送miR-140的载体材料具有良好应用前景。此外,CPCs主要分散在软骨表层,而OA软骨损伤也开始于该层,因此强调OA早期干预至关重要。结论 miR-140具有诱导活化CPCs、促进OA早期软骨损伤修复的潜能,进一步探索miR-140在OA发生机制中的作用及研发基于miR-140的新的OA治疗策略具有重要临床意义。
Objective To summarize the effect of cartilage progenitor cells(CPCs) and microRNA-140(miR-140) on the repair of osteoarthritic cartilage injury, and analyze their clinical prospects. Methods The recent researches regarding the CPCs, miR-140, and repair of cartilage in osteoarthritis(OA) disease were extensively reviewed and summarized. Results CPCs possess the characteristics of self-proliferation, expression of stem cell markers, and multilineage differentiation potential, and their chondrogenic ability is superior to other tissues-derived mesenchymal stem cells. CPCs are closely related to the development of OA, but the autonomic activation and chondrogenic ability of CPCs around the osteoarthritic cartilage lesion cannot meet the requirements of complete cartilage repair. miR-140 specifically express in cartilage, and has the potential to activate CPCs by inhibiting key molecules of Notch signaling pathway and enhance its chondrogenic ability, thus promoting the repair of osteoarthritic cartilage injury. Intra-articular delivery of drugs is one of the main methods of OA treatment, although intra-articular injection of miR-140 has a significant inhibitory effect on cartilage degeneration in rats, it also exhibit some limitations such as non-targeted aggregation, low bioavailability, and rapid clearance. So it is a good application prospect to construct a carrier with good safety, cartilage targeting, and high-efficiency for miR-140 based on articular cartilage characteristics. In addition, CPCs are mainly dispersed in the cartilage surface, while OA cartilage injury also begins from this layer, it is therefore essential to emphasize early intervention of OA. Conclusion miR-140 has the potential to activate CPCs and promote the repair of cartilage injury in early OA, and it is of great clinical significance to further explore the role of miR-140 in OA etiology and to develop new OA treatment strategies based on miR-140.
作者
斯海波
梁明玮
程惊秋
沈彬
SI Haibo;LIANG Mingwei;CHENG Jingqiu;SHEN Bin(Department of Orthopedics, West China Hospital, Sichuan University, Chengdu Sichuan, 610041, P.R.China)
出处
《中国修复重建外科杂志》
CAS
CSCD
北大核心
2019年第5期650-656,共7页
Chinese Journal of Reparative and Reconstructive Surgery
基金
国家自然科学基金资助项目(81802210)
四川省科技厅重点研发计划项目(2018SZ0223
2018SZ0250)
中国博士后科学基金第61批面上项目(2017M610604)~~
