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Published on: June 2, 2023
MiR-140-3p Ameliorates the Progression of Osteoarthritis via Targeting CXCR4
Tiantian Ren1,2, Peng Wei1, Qinghua Song1
1Department of Orthopaedics, Ningbo First Hospital.
Abstract:
Osteoarthritis is a common disease character with progressive destruction of cartilage. MicroRNA (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 quantitative real time (qRT)-PCR. In vitro osteoarthritis model was established by treatment of the chondrocyte cells CHON-001 with interleukin (IL)-1β. Cell proliferation and apoptosis were measured with cell counting kit-8 (CCK8) and Annexin V/propidium iodide (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 matrix metalloproteinase (MMP)13. 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.
Insights
MicroRNA-140-3p, a biomarker for osteoarthritis, suppresses disease progression by targeting CXCR4. This microRNA may offer a new therapeutic strategy for osteoarthritis treatment.
Area of Science:
- Biochemistry
- Molecular Biology
- Cell Biology
Background:
- Osteoarthritis is characterized by progressive cartilage destruction.
- MicroRNA (miR)-140-3p is a validated biomarker for osteoarthritis, but its regulatory mechanism is unclear.
Purpose of the Study:
- To evaluate the function of miR-140-3p in osteoarthritis pathogenesis.
- To investigate the potential of miR-140-3p as a therapeutic target.
Main Methods:
- Quantitative real-time PCR (qRT-PCR) for miR-140-3p expression.
- In vitro osteoarthritis model using interleukin (IL)-1β stimulation of chondrocytes.
- Cell proliferation (CCK8) and apoptosis (Annexin V/PI) assays.
- Western blot for protein expression and luciferase reporter assay for target validation.
Main Results:
- miR-140-3p was downregulated in osteoarthritis knee tissue.
- IL-1β inhibited chondrocyte proliferation, induced apoptosis, decreased collagen II and aggrecan, and increased MMP13.
- miR-140-3p mimics ameliorated IL-1β effects and blocked IL-1β-induced CXCR4 upregulation.
- CXCR4 was identified as a direct target gene of miR-140-3p.
Conclusions:
- miR-140-3p suppresses osteoarthritis progression by directly targeting CXCR4.
- miR-140-3p holds potential as a therapeutic target for osteoarthritis treatment.

