Let-7a-5p derived from parathyroid hormone (1–34)-preconditioned BMSCs exosomes delays the progression of osteoarthritis by promoting chondrocyte proliferation and migration

作者：Litao Shao, Lu Ding, Weizhao Li, Chi Zhang, Yu Xia, Miaoyu Zeng, Zhizhong Ye, David Y.B. Deng · 发表于：Stem Cell Research & Therapy · 年份：2025 · DOI：10.1186/s13287-025-04416-0 · 被引用次数：10 · 研究领域：Osteoarthritis Treatment and Mechanisms、Mesenchymal stem cell research、Extracellular vesicles in disease

Osteoarthritis (OA) is a prevalent degenerative joint disorder affecting over 240 million people worldwide, yet no disease-modifying therapies currently exist, with clinical management limited to symptomatic relief or joint replacement. Exosomes (Exos) from bone marrow mesenchymal stem cells (Exo BMSC ) play positive role in the treatment of cartilage damage. Parathyroid hormone (PTH) (1–34) can enhance cartilage repair. Here, We found Exos from Exo BMSC reduces cartilage damage during treatment. Meanwhile, the Exos of PTH(1–34)-preconditioned BMSCs (Exo PTH ) can alleviate OA better than Exo BMSC . Through MicroRNA (miRNA) sequencing analysis, this study aims to reveal the effects and potential mechanism of miRNA (let-7a-5p) in Exo PTH to repair OA cartilage. Differential centrifugation was used for isolating Exo BMSC and Exo PTH . Extract bone marrow mesenchymal stem cells from rats and utilize the C28/I2 chondrocytes line, the OA model was established using lipopolysaccharide (LPS; 1 µg/mL) in vitro. OA was induced in rats with intra-articular injection with collagenase-2. By performing a miRNA array, RNA-seq, in addition to bioinformatic analysis, the miRNA and the potential regulatory mechanism were detected. We compared in vitro let-7a-5p effects on the ability of OA chondrocytes to proliferate, migrate, apoptosis, and form the extracellular matrix (ECM). Histological and immunohistochemical assessments were used for evaluating cartilage pathology in vivo. We extracted ...