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miR‑486‑5p is upregulated in osteoarthritis and inhibits chondrocyte proliferation and migration by suppressing SMAD2
Junkai Shi1, Kansuo Guo1, Shile Su2
1Department of Orthopedics, Lianyungang Oriental Hospital, Lianyungang, Jiangsu 222042, P.R. China.
Abstract:
Osteoarthritis (OA) is the most common form of arthritis and is caused by the breakdown of joint cartilage. The present study aimed to investigate an effective method for the treatment of OA. It was demonstrated that, compared with other patients, patients with OA exhibited lower mRNA expression levels of SMAD family member 2 (SMAD2). MicroRNA (miR)‑486‑5p was predicted to bind with SMAD2, which was verified by dual‑luciferase reporter assay. Compared withcontrol patients who had no known history of OA or rheumatoid arthritis, patients with OA exhibited higher miR‑486‑5p expression level. Treatment with miR‑486‑5p mimics inhibited proliferation and migration of CHON‑001 human chondrocytes, and also inhibited the expression levels of type II collagen and aggrecan. However, treatment with a miR‑486‑5p inhibitor promoted proliferation and migration, and the expression of type II collagen and aggrecan. Short interfering RNA‑directed silencing of SMAD2 reversed the upregulated proliferation and migration and the expression level of type II collagen and aggrecan induced by the miR‑486‑5p inhibitor. In conclusion, the results of the present study indicated that miR‑486‑5p was upregulated in OA and may inhibit chondrocyte proliferation and migration by suppressing SMAD2.
Insights
Osteoarthritis patients show higher levels of miR-486-5p, which suppresses SMAD2. This microRNA may inhibit chondrocyte proliferation and migration, offering a potential therapeutic target for osteoarthritis.
Area of Science:
- Biomedical research
- Molecular biology
- Orthopedics
Background:
- Osteoarthritis (OA) is a prevalent degenerative joint disease characterized by cartilage breakdown.
- Understanding the molecular mechanisms underlying OA pathogenesis is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the role of microRNA (miR)-486-5p and SMAD family member 2 (SMAD2) in osteoarthritis (OA).
- To explore the potential of targeting the miR-486-5p/SMAD2 pathway for OA treatment.
Main Methods:
- Analysis of SMAD2 mRNA expression in OA patients.
- Validation of the interaction between miR-486-5p and SMAD2 using dual-luciferase reporter assays.
- In vitro experiments using chondrocytes treated with miR-486-5p mimics, inhibitors, and SMAD2-targeting short interfering RNA (siRNA).
- Assessment of chondrocyte proliferation, migration, and expression of type II collagen and aggrecan.
Main Results:
- Patients with OA exhibited lower SMAD2 mRNA expression and higher miR-486-5p expression compared to controls.
- miR-486-5p mimics inhibited chondrocyte proliferation, migration, and expression of type II collagen and aggrecan.
- miR-486-5p inhibition promoted chondrocyte proliferation and migration, and increased type II collagen and aggrecan expression.
- SMAD2 silencing reversed the effects induced by miR-486-5p inhibition, indicating SMAD2 is a downstream target.
Conclusions:
- miR-486-5p is upregulated in osteoarthritis.
- miR-486-5p may exert its effects in OA by suppressing SMAD2, thereby inhibiting chondrocyte proliferation and migration.
- The miR-486-5p/SMAD2 axis represents a potential therapeutic target for osteoarthritis.
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