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Updated: Aug 3, 2025
Software-Assisted Quantitative Measurement of Osteoarthritic Subchondral Bone Thickness
Published on: March 18, 2022
Inhibition of miR-182-5p Targets FGF9 to Alleviate Osteoarthritis
Yang Sun1, Sanmao Su2, Mengjun Li1
1Department of Spine Surgery and Orthopaedics, Xiangya Hospital Central South University, Changsha, China.
Background:
The pathogenesis of osteoarthritis (OA) is complex and there is no specific drug for treatment. The aim of this study was to identify the molecular targets of OA therapy, focusing on the expression and biological functions of miR-182-5p and its target genes in OA.
Methods:
miR-182-5p and fibroblast growth factor 9 (FGF9) were overexpressed or knocked down in IL-1β-induced chondrocytes. An OA knee model was performed by surgically destroying the medial meniscus. The gene expression of miR-182-5p and FGF9 was calculated. The protein FGF9 was tested by western blotting. Cell counting kit-8 (CCK8), plate cloning assay, and flow cytometry were conducted to evaluate cell proliferation and apoptosis. The expression of inflammatory factors, tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, and interleukin (IL)-8, was evaluated using enzyme-linked immunosorbent assay (ELISA). Dual-luciferase reporter assays validated the targeting relationship between miR-182-5p and FGF9. Hematoxylin-eosin (HE) and safranin O-fast Green (S-O) staining were utilized to access cartilage damage. Ki67 expression in cartilage was detected using immunohistochemistry (IHC). TdT-mediated dUTP nick-end labeling (TUNEL) assays were used to calculate the apoptosis rate of cartilage.
Results:
The expression of miR-182-5p was upregulated, and FGF9 was downregulated in the IL-1β-induced chondrocytes. OA chondrocytes proliferation ability in the miR-182-5p mimics group was decreased, and the apoptosis rate and inflammatory factor were increased. Transfection with miR-182-5p inhibitor increased the proliferative ability and decreased the apoptosis rate in the IL-1β-induced chondrocytes. Transfection with miR-182-5p inhibitor reversed IL-1β-induced inflammatory factor release in chondrocytes. Targeted binding sites existed between miR-182-5p and FGF9. After overexpression of FGF9, the miR-182-5p effect on OA chondrocytes was reversed. The hyaline cartilage thickness and proteoglycan content decreased in OA rats, and this was reversed by miR-182-5p inhibitor treatment.
Conclusions:
miR-182-5p expression levels were increased in OA chondrocytes and regulated chondrocyte proliferation, apoptosis, and inflammation by targeting FGF9. miR-182-5p is a potential gene for OA treatment.
Insights
MicroRNA-182-5p (miR-182-5p) is upregulated in osteoarthritis (OA) and targets fibroblast growth factor 9 (FGF9), influencing chondrocyte behavior. Inhibiting miR-182-5p shows potential for OA therapy by restoring cartilage health.
Area of Science:
- Molecular Biology
- Biochemistry
- Cell Biology
Background:
- Osteoarthritis (OA) pathogenesis is complex with no targeted therapies.
- Identifying molecular targets is crucial for developing effective OA treatments.
Purpose of the Study:
- To investigate the role of miR-182-5p and its target genes in osteoarthritis.
- To evaluate miR-182-5p as a potential therapeutic target for OA.
Main Methods:
- Utilized IL-1β-induced chondrocytes and an OA rat model.
- Assessed miR-182-5p and FGF9 expression, chondrocyte proliferation, apoptosis, and inflammation.
- Validated the miR-182-5p and FGF9 interaction using dual-luciferase reporter assays.
Main Results:
- miR-182-5p was upregulated, and FGF9 downregulated in OA chondrocytes.
- miR-182-5p inhibition increased proliferation, decreased apoptosis and inflammation in chondrocytes.
- miR-182-5p inhibitor treatment reversed cartilage damage in OA rats.
Conclusions:
- miR-182-5p regulates chondrocyte proliferation, apoptosis, and inflammation by targeting FGF9 in OA.
- miR-182-5p represents a promising therapeutic target for osteoarthritis treatment.
