Qin Shangzhu, Zhang Aijie, Duan Lian, Lin Fang, Zhao Mingcai
Department of Laboratory Medicine, North Sichuan Medical College, Nanchong, 637100, China.
Basic Laboratory, Suining Central Hospital, Suining, 629000, China.
Tissue Eng Regen Med. 2025 Apr 15. doi: 10.1007/s13770-025-00716-x.
Osteoarthritis (OA), a widespread chronic joint disorder mainly affecting the elderly, currently lacks a definitive cure. This study investigated the efficacy of exosomes (Exos) extracted from human umbilical cord MSCs (hucMSCs) in the treatment of OA, and preliminarily explored the mechanisms.
A rat osteoarthritis model was constructed by surgical induction. The cartilage morphology was observed after pathological staining; expression of cartilage matrix protein, autophagy-related protein and β-catenin were detected by immunohistochemistry; and inflammatory factors in serum were tested by ELISA. In cellular experiments, human primary chondrocytes were induced with IL-1β to build the OA microenvironment. The levels of relevant proteins in each group were analyzed.
Comparing to the OA model, the Exos treatment showed positive effects in reducing OARSI score and Mankin score, decreasing joint space stenosis, promoting matrix synthesis, increasing autophagy, and decreasing β-catenin. The results of the cellular experiments were consistent with those from the animal experiments. However, the Wnt/β-catenin pathway was greatly activated, the levels of matrix proteins and autophagy were distinctly reduced in the Exos + LiCl group comparing to the exosome-treated group.
hucMSCs-Exos effectively attenuated the pathological damage of OA cartilage and chondrocytes, promoted the synthesis of cartilage matrix, reduced inflammation, suppressed the Wnt/β-catenin pathway, and enhanced autophagy which promoted the repair of OA cartilage.
骨关节炎(OA)是一种主要影响老年人的广泛存在的慢性关节疾病,目前缺乏确切的治愈方法。本研究调查了从人脐带间充质干细胞(hucMSCs)中提取的外泌体(Exos)在治疗OA中的疗效,并初步探讨了其机制。
通过手术诱导构建大鼠骨关节炎模型。病理染色后观察软骨形态;通过免疫组织化学检测软骨基质蛋白、自噬相关蛋白和β-连环蛋白的表达;通过酶联免疫吸附测定法检测血清中的炎症因子。在细胞实验中,用白细胞介素-1β诱导人原代软骨细胞构建OA微环境。分析每组中相关蛋白的水平。
与OA模型相比,Exos治疗在降低骨关节炎研究学会(OARSI)评分和曼金(Mankin)评分、减少关节间隙狭窄、促进基质合成、增加自噬以及降低β-连环蛋白方面显示出积极作用。细胞实验结果与动物实验结果一致。然而,与外泌体治疗组相比,Exos+氯化锂(LiCl)组中Wnt/β-连环蛋白通路被极大激活,基质蛋白水平和自噬明显降低。
hucMSCs-Exos有效减轻了OA软骨和软骨细胞的病理损伤,促进了软骨基质的合成,减轻了炎症,抑制了Wnt/β-连环蛋白通路,并增强了自噬,从而促进了OA软骨的修复。