MiR-140-3p Ameliorates the Progression of Osteoarthritis via Targeting CXCR4
Open Access
- 1 May 2020
- journal article
- research article
- Published by Pharmaceutical Society of Japan in Biological & Pharmaceutical Bulletin
- Vol. 43 (5), 810-816
- https://doi.org/10.1248/bpb.b19-00959
Abstract
Osteoarthritis is a common disease character with progressive destruction of cartilage. MiR-140-3p was validated as a biomarker for osteoarthritis. However, the mechanism by which miRNA-140-3p regulates osteoarthritis remains unclear. Thus, this study aims to evaluate the potential function of miRNA-140-3p during the pathogenesis of osteoarthritis. MiRNA-140-3p expression in tissue and CHON-001 chondrocyte cells was determined with qRT-PCR. In vitro osteoarthritis model was established by treatment of the chondrocyte cells CHON-001 with IL-1β. Cell proliferation and apoptosis were measured with CCK8 and Annexin V/PI apoptosis assay, respectively. Protein expressions were evaluated using western blot. The target gene of miR-140-3p was predicted using Targetscan and miRDB. MiR-140-3p was downregulated in knee tissue from patients with osteoarthritis. IL-1β inhibited the proliferation of CHON-001 cells via inducing apoptosis. In addition, IL-1β significantly inhibited the expressions of collagen II and aggrecan and increased the level of MMP13. However, the effects of IL-1β could be ameliorated by the addition of miR-140-3p mimics. Moreover, luciferase reporter assay demonstrated CXCR4 as a target gene of miR-140-3p. IL-1β-induced upregulation of CXCR4 could be blocked by miR-140-3p mimics. Our study indicated that miR-140-3p could suppress the progression of osteoarthritis by directly targeting CXCR4. Therefore, miR-140-3p might serve as a potential therapeutic target for the treatment of osteoarthritis.Keywords
This publication has 23 references indexed in Scilit:
- MicroRNA-21 controls the development of osteoarthritis by targeting GDF-5 in chondrocytesExperimental & Molecular Medicine, 2014
- Attenuation of osteoarthritis via blockade of the SDF-1/CXCR4 signaling pathwayArthritis Research & Therapy, 2012
- microRNA-150 Regulates Mobilization and Migration of Bone Marrow-Derived Mononuclear Cells by Targeting Cxcr4PLOS ONE, 2011
- MiR-140 is co-expressed withWwp2-Ctranscript and activated by Sox9 to targetSp1in maintaining the chondrocyte proliferationFEBS Letters, 2011
- Stimulation of chondrocyte hypertrophy by chemokine stromal cell-derived factor 1 in the chondro-osseous junction during endochondral bone formationDevelopmental Biology, 2010
- MicroRNA‐27b regulates the expression of matrix metalloproteinase 13 in human osteoarthritis chondrocytesArthritis & Rheumatism, 2010
- Aging-related loss of the chromatin protein HMGB2 in articular cartilage is linked to reduced cellularity and osteoarthritisProceedings of the National Academy of Sciences of the United States of America, 2009
- Cartilage homeostasis in health and rheumatic diseasesArthritis Research & Therapy, 2009
- Integrative MicroRNA and Proteomic Approaches Identify Novel Osteoarthritis Genes and Their Collaborative Metabolic and Inflammatory NetworksPLOS ONE, 2008
- Development of criteria for the classification and reporting of osteoarthritis: Classification of osteoarthritis of the kneeArthritis & Rheumatism, 1986