骨性关节炎靶向基因治疗的研究进展△

Research progress in targeted gene therapy for osteoarthritis

摘要:

骨性关节炎（osteoarthritis, OA）是常见的关节退行性疾病，其病理改变累及关节软骨、软骨下骨、韧带、关节囊和滑膜，主要表现为进行性软骨退变和继发性骨质增生。早期 OA 可选择运动、药物等治疗方式，病情加重时，则需要手术治疗。随着人类基因组信息不断揭示，为解决 OA 提供了新的思路。基因治疗借助病毒或非病毒载体将目的基因导入退变关节腔，使目的基因能够在关节稳定、可控、靶向的表达，通过减轻关节局部炎症、抑制软骨基质降解和促进软骨基质合成等方式，保护和修复受损的软骨。本文就 OA 基因治疗对炎症及软骨基质代谢的影响、基因递送系统、小核糖核酸 （micro ribonu- cleic acid, miRNA） 及长非编码核糖核酸 （long non-coding ribonucleic acid, LncRNA） 等方面进行综述，为未来相关研究提供参考。

Abstract:

Osteoarthritis (OA) is a common joint degenerative disease with pathological changes involving articular cartilage, subchondral bone, ligaments, joint capsule and synovium. Its main manifestations are progressive cartilage degeneration and secondary hyperostosis. Early treatment options for OA include exercise and medication, but when the condition worsens, surgical treatment is required. With the continuous disclosure of human genome information, gene therapy provides a new way to solve OA. Gene therapy utilizes viral or non-viral vectors to transfer target genes into the degenerative joint cavity, enabling stable, controllable and targeted expression of target genes in joints. By reducing local inflammation, inhibiting cartilage matrix degradation and promoting cartilage matrix synthesis, gene therapy protects and repairs damaged cartilage. This article reviews the effects of OA gene therapy on inflammation and cartilage matrix metabolism, gene delivery systems, micro ribonucleic acid (microRNA) and long non-coding ribonucleic acid (LncRNA) related to this field.