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外体
化学
细胞凋亡
成纤维细胞
细胞生物学
软骨
微泡
癌症研究
分子生物学
小RNA
基因表达
生物
基因
生物化学
解剖
体外
作者
Guangxuan Zeng,Gang Deng,Shuai Xiao,Fēi Li
标识
DOI:10.1080/08820139.2021.1936010
摘要
Background: Long non-coding RNA (lncRNA) prostate cancer gene expression marker 1 (PCGEM1) has been revealed to participate in the pathogenesis of osteoarthritis (OA). However, the molecular mechanism of PCGEM1 regulating OA progression has not been fully elucidated.Methods: Fibroblast-like synoviocytes (FLSs) were isolated from synovium tissues of OA patients (OA-FLSs) and trauma donors (Normal-FLSs). The size and morphology of the isolated exosomes were analyzed by transmission electron microscopy and nanoparticle tracking analysis. Protein levels were analyzed by western blotting. Expression levels of PCGEM1, microRNA-142-5p (miR-142-5p), runt-related transcription factor 2 (RUNX2) mRNA, and OA related genes were assessed by qRT-PCR. Cell proliferation, viability, and apoptosis were evaluated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide or flow cytometry assays. The relationship between miR-142-5p and PCGEM1 or RUNX2 was verified by dual-luciferase reporter and/or RNA pull down assays.Results: PCGEM1 was overexpressed in OA cartilages and exosomes from OA-FLSs. Exosomal PCGEM1 from OA-FLSs facilitated IL-1β-induced apoptosis and cartilage matrix degradation in chondrocytes. MiR-142-5p was downregulated while RUNX2 was upregulated in OA cartilages. Exosomal PCGEM1 from OA-FLSs regulated RUNX2 expression by sponging miR-142-5p in IL-1β-induced chondrocytes. MiR-142-5p inhibitor offset exosomal PCGEM1 knockdown-mediated effects on the apoptosis and cartilage matrix degradation of IL-1β-induced chondrocytes. RUNX2 overexpression counteracted the suppressive effect of miR-142-5p mimic on apoptosis and cartilage matrix degradation of IL-1β-induced chondrocytes.Conclusion: Exosomal PCGEM1 from OA-FLSs facilitated IL-1β-induced apoptosis and cartilage matrix degradation in chondrocytes by sequestering miR-142-5p and upregulating RUNX2, which offered new insights into the pathogenesis of OA.
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