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| 基质金属蛋白酶13在靶向治疗骨关节炎的研究进展 |
| Research progress on the treatment of osteoarthritis by targeting matrix metalloproteinase 13 |
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| DOI：10.3969/j.issn.1006-7108.2024.03.018 |
| 中文关键词: 骨关节炎 基质金属蛋白酶13 MMP13抑制剂 小干扰RNA 基因编辑 |
| 英文关键词:osteoarthritis matrix metalloproteinase 13 MMP13 inhibitors small interfering RNA gene editing |
| 基金项目:国家自然科学基金(81860401)；内蒙古自治区科技厅重点项目(2022YFSH0075) |
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| 中文摘要: |
| 骨关节炎（osteoarthritis , OA）是一类常见的慢性退行性疾病，可导致关节软骨、滑膜、软骨下骨等多组织损伤。目前，该疾病的发病机制尚未完全阐明。研究发现基质金属蛋白酶（matrix metalloproteinase，MMPs）与该疾病的发病过程相关，特别是MMP13，其在机体内的表达水平与OA关系密切。近年来，针对MMP13在该疾病发生发展中的作用，靶向MMP13治疗OA具有诸多进展，选择性MMP13抑制剂较广谱MMPs抑制剂具有选择性强、毒副作用低、效能高等优点，但需要频繁给药以维持药物在体内的有效浓度；将与MMP13 mRNA具有选择性互补的小干扰RNA注射入关节腔可有效降低体内MMP13蛋白产生并抑制多种炎症因子表达，且单次注射可较长时间维持药物效果；利用CRISPR-Cas9基因编辑技术靶向消融MMP13基因以减弱软骨细胞外基质蛋白的降解从而治疗OA的方式在动物体内外模型中均具有较好效果，但该技术在人体内长期应用的安全性也引发人们的思考。靶向MMP13治疗OA是医学界及科研领域的重要研究方向，未来结合更前沿的生物医学技术将为探索治疗OA提供新的策略。 |
| 英文摘要: |
| Osteoarthritis (OA) is a common chronic degenerative disease, which can lead to multiple tissue injuries such as articular cartilage, synovial membrane and subchondral bone. At present, the pathogenesis of the disease is not fully understood. Studies have found that Matrix metalloproteinase (MMPs) is related to the pathogenesis of the disease, especially MMP13, which expression level in the body is closely related to OA. In recent years, in view of the role of MMP13 in the occurrence and development of this disease, there has been some progress in the treatment of OA by targeting MMP13. Compared with broad-spectrum MMPs inhibitors, selective MMP13 inhibitors have some advantages such as strong selectivity, low toxicity and high efficacy, but frequent administration is required to maintain the effective concentration of the drug in vivo; injection of small interfering RNA that is selectively complementary to MMP13mRNA into the joint cavity can effectively reduce the production of MMP13 protein and inhibit the expression of various inflammatory factors in vivo, and a single injection can maintain the drug effect for a long time; the use of CRISPR-Cas9 gene editing technology to target the ablation of MMP13 gene to weaken the degradation of chondrocyte extracellular matrix protein in the treatment of OA has good effects on animal models both in vivo and in vitro, but the long-term safety of this technology in human beings has also triggered people's thinking. Targeted MMP13 treatment of OA is an important research direction in the medical field and scientific research field, and the combination of more advanced cutting-edge biomedical technologies in the future will provide a new strategy for exploring the treatment of OA. |
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