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MiR-379-5p Promotes Chondrocyte Proliferation via Inhibition of PI3K/Akt Pathway by Targeting YBX1 in Osteoarthritis

OBJECTIVE: We evaluated the ability of miR-379-5p to influence the proliferation of osteoarthritis chondrocytes and elucidated the regulatory mechanism of miR-379-5p in osteoarthritis. METHODS: Real time polymerase chain reaction (RT- PCR) was used to detect the expression of miR-379-5p and YBX1 in...

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Detalles Bibliográficos
Autores principales: Zhang, Hongjun, Zheng, Wendi, Li, Du, Zheng, Jia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9137300/
https://www.ncbi.nlm.nih.gov/pubmed/35255737
http://dx.doi.org/10.1177/19476035221074024
Descripción
Sumario:OBJECTIVE: We evaluated the ability of miR-379-5p to influence the proliferation of osteoarthritis chondrocytes and elucidated the regulatory mechanism of miR-379-5p in osteoarthritis. METHODS: Real time polymerase chain reaction (RT- PCR) was used to detect the expression of miR-379-5p and YBX1 in knee articular cartilages of human. Cell proliferation, inflammatory factors, extracellular matrix (ECM) degradation-associated proteins and proteins in PI3K/Akt pathway were assessed in rat primary chondrocytes treated with interleukin (IL)-1β or/and miR-379-5p mimics or miR-379-5p inhibitor via cell counting assay kit-8 (CCK-8), enzyme-linked immunosorbent assay (ELISA), immunofluorescence and Western blotting (WB). The target of miR-379-5p predicted by TargetScan and miRwalk software was verified by luciferase reporter assay. Safranin O-fast green staining, immunohistochemistry, and WB were performed to observe the effect of miR-379-5p agomir on development of osteoarthritis in rats. RESULTS: MiR-379-5p was down-regulated in human osteoarthritic tissues and negatively correlated with YBX1 expression. High level of miR-379-5p in chondrocytes with IL-1β stimulated increased cell viability, the expression of proliferation-related protein and extracellular matrix (ECM)-related proteins collagen II and aggrecan. However, the expression of inflammatory factors and ECM-related proteins matrix metalloproteinases (MMP-1) and MMP-13 was decreased. Luciferase reporting assay verified the targeting relationship between miR-379-5p and YBX1. This function of miR-379-5p was exerted through PI3K/Akt pathway and could be blocked by the PI3K/Akt pathway inhibitor LY294002. MiR-379-5p agomir promoted the articular chondrocytes proliferation and alleviated cartilage degradation in vivo. CONCLUSION: Our findings reveal that miR-379-5p can promote the articular chondrocytes proliferation in osteoarthritis (OA) by interacting with YBX1 and regulating PI3K/Akt pathway. Restoring miR-379-5p might be a future therapeutic strategy for OA.