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Published on: February 24, 2017
miR-137 suppresses cell growth and extracellular matrixdegradation through regulating ADAMTS-5 in chondrocytes
Yuanmin Zhang1, Guodong Wang1, Longfei Ma1
1Department of Orthopedics, Affiliated Hospital of Jining Medical University Jining 272029, Shandong, China.
Abstract:
Osteoarthritis (OA) is the most common degenerative joint disease. microRNAs (miRNAs) have been showen to act critical roles in several diseases including OA. However, the involvement and underlying mechanism of miR-137 in development of OA remains unkown. In our study, we firstly showed that IL-1β decreased the expression of miR-137 in the chondrocytes and we demonstrated that the miR-37 expression level was lower in the OA cases than in the control patients. Dual-luciferase reporter analysis was performed to confirm that ADAMTS-5 was a direct target gene of miR-137. Furthermore, we indicated that elevated expression of miR-137 decreased the protein expression of ADAMTS-5 in the chondrocytes. In additional, we showed that IL-1β induces the ADAMTS-5 expression in the chondrocytes. The ADAMTS-5 expression level was higher in the OA cases than in the control patients. We showed that the expression of ADAMTS-5 was negatively correlated with the miR-137 expression level in OA tissues. Overexpression of miR-137 suppressed cell growth, extracellular matrix (ECM) degradation and inflammation in chondrocytes. These preliminary data elucidated that miR-137 suppressed OA progression via inhibiting cell growth, inflammation and ECM degradation.
Insights
MicroRNA-137 (miR-137) plays a crucial role in osteoarthritis (OA) by suppressing chondrocyte growth, inflammation, and extracellular matrix degradation, offering a potential therapeutic target.
Area of Science:
- Biochemistry
- Molecular Biology
- Rheumatology
Background:
- Osteoarthritis (OA) is a prevalent degenerative joint disease.
- MicroRNAs (miRNAs) are implicated in various diseases, including OA.
- The specific role and mechanism of miR-137 in OA pathogenesis are largely unknown.
Purpose of the Study:
- To investigate the involvement and mechanism of miR-137 in the development of osteoarthritis.
- To determine if miR-137 targets ADAMTS-5 and affects its expression.
- To elucidate the effect of miR-137 on chondrocyte function and OA progression.
Main Methods:
- Assessing miR-137 expression in chondrocytes and OA patient tissues.
- Utilizing dual-luciferase reporter assays to identify miR-137 targets.
- Overexpressing miR-137 in chondrocytes to evaluate its functional impact.
- Measuring cell growth, extracellular matrix degradation, and inflammation markers.
Main Results:
- Interleukin-1 beta (IL-1β) reduced miR-137 expression in chondrocytes.
- miR-137 expression was significantly lower in OA patients compared to controls.
- ADAMTS-5 was identified as a direct target of miR-137.
- Elevated miR-137 expression decreased ADAMTS-5 protein levels and suppressed OA-related cellular processes.
- ADAMTS-5 expression was higher in OA tissues and negatively correlated with miR-137 levels.
Conclusions:
- miR-137 acts as a suppressor of osteoarthritis progression.
- The mechanism involves inhibiting chondrocyte proliferation, extracellular matrix degradation, and inflammation.
- miR-137 targets ADAMTS-5, a key enzyme in matrix degradation.
- These findings highlight miR-137 as a potential therapeutic target for OA.
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