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Exosomal miR-429 derived from adipose-derived stem cells ameliorated chondral injury in osteoarthritis via autophagy by targeting FEZ2

自噬 骨关节炎 化学 脂肪组织 癌症研究 药理学 医学 病理 内科学 细胞凋亡 生物化学 替代医学
作者
Chenyang Meng,Yuyan Na,Changxu Han,Yizhong Ren,Ming Liu,Penglei Ma,Rui Bai
出处
期刊:International Immunopharmacology [Elsevier]
卷期号:120: 110315-110315 被引量:15
标识
DOI:10.1016/j.intimp.2023.110315
摘要

Osteoarthritis (OA) is the most prevalent musculoskeletal disease, imposing a significant public health burden. Exosomes might be an effective means of treating OA. To investigate the role of exosomes from adipose tissue-derived stromal cells (ADSCs) in OA. We explored whether exosomes from ADSCs could be absorbed by OA chondrocytes, whether there were differences in miR-429 expression in the exosomes of ADSCs and chondrocytes, and whether ADSC exosomal miR-429 could enhance chondrocyte proliferation to exert therapeutic effects in OA. Controlled laboratory study. ADSCs were isolated and cultured from 4-week-old Sprague-Dawley rats. ADSCs and chondrocytes were identified by flow cytometry assay and fluorescent staining, respectively. The exosomes were extracted and identified. Exosome transport was verified by cell staining and co-culture. Beclin 1, collagen II, LC3-II/I, miR-429, and FEZ2 mRNA and protein expression were investigated with real-time PCR and western blotting, respectively. Chondrocyte proliferation was investigated with Cell Counting Kit-8 (CCK-8) assay. The association between miR-429 and FEZ2 was verified with luciferase assay. A rat OA model was established and rat knee joint cartilage tissue was examined with hematoxylin–eosin and toluidine blue staining. Both ADSCs and chondrocytes secreted exosomes and ADSC-derived exosomes could be absorbed by the chondrocytes. ADCS exosomes contained higher miR-429 levels than chondrocyte exosomes. The luciferase assay demonstrated that miR-429 directly targeted FEZ2. Compared with the OA group, miR-429 promoted chondrocyte proliferation while FEZ2 decreased it. miR-429 promoted autophagy by targeting FEZ2 to ameliorate cartilage injury. In vivo, miR-429 promoted autophagy to alleviate OA by targeting FEZ2. ADSC exosomes could be beneficial for OA and could be absorbed by chondrocytes to promote chondrocyte proliferation through miR-429. miR-429 ameliorated cartilage injury in OA by targeting FEZ2 and promoting autophagy.
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