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Updated: Jul 26, 2025
Destabilization of the Medial Meniscus and Cartilage Scratch Murine Model of Accelerated Osteoarthritis
Published on: July 6, 2022
Knockdown of circSOD2 ameliorates osteoarthritis progression via the miR-224-5p/PRDX3 axis
Hao Li1, Yong Cao2, Chongfei Chang3
1Department of Sports Medicine, Shenzhen Second People's Hospital, Shenzhen, 518037, Guangdong, China.
Background:
Although the implications of circular RNAs (circRNAs) with the progression of diverse pathological conditions have been reported, the circRNA players in osteoarthritis (OA) are barely studied.
Methods:
In this study, twenty-five OA patients who received arthroplasty were recruited for cartilage tissue collection. Public circRNA microarray data from Gene Expression Omnibus was retrieved for circRNA identification. An in vitro cell model of OA-related damages was constructed by treating human chondrocytes (CHON-001 cell line) with IL-1β, and circSOD2 siRNA was used to silence circSOD2 expression to study its functional role in apoptosis, inflammatory responses, and extracellular matrix (ECM) degradation. Besides, we investigated the functional interactions among circSOD2, miR-224-5p, and peroxiredoxin 3 (PRDX3) by luciferase reporter assay, RNA-immunoprecipitation assay, and quantitative reverse transcription polymerase chain reaction.
Results:
Our findings revealed the overexpression of circSOD2 in the OA cartilage and cell samples, and circSOD2 knockdown alleviated ECM degradation, inflammation, and apoptosis in CHON-001 cell model. In addition, our findings suggested the regulatory function of circSOD2 knockdown on miR-224-5p expression, while miR-224-5p was capable of downregulating PRDX3 expression. The co-transfection of miR-224-5p inhibitor or pcDNA-PRDX3 could prevent the effect of circSOD2 knockdown.
Conclusion:
Hence, our results demonstrated that knockdown of circSOD2 may serve as an intervention strategy to alleviate OA progression through modulating miR-224-5p/PRDX3 signaling axis.
Insights
Circular RNAs (circRNAs) are implicated in diseases, but their role in osteoarthritis (OA) is unclear. This study shows circSOD2 knockdown alleviates OA progression by targeting the miR-224-5p/PRDX3 pathway.
Area of Science:
- Biochemistry
- Molecular Biology
- Genetics
Background:
- Circular RNAs (circRNAs) are increasingly recognized for their roles in various pathological conditions.
- However, the specific involvement of circRNAs in the development and progression of osteoarthritis (OA) remains largely unexplored.
Purpose of the Study:
- To investigate the role of circSOD2 in osteoarthritis.
- To elucidate the molecular mechanism underlying circSOD2's function in OA, focusing on its interaction with miR-224-5p and PRDX3.
Main Methods:
- Collected cartilage tissue from OA patients undergoing arthroplasty.
- Utilized public circRNA microarray data for identification.
- Established an in vitro OA cell model using human chondrocytes treated with IL-1β.
- Performed circSOD2 knockdown experiments and analyzed apoptosis, inflammation, and extracellular matrix (ECM) degradation.
- Investigated molecular interactions using luciferase reporter assays, RNA-immunoprecipitation, and qRT-PCR.
Main Results:
- Overexpression of circSOD2 was observed in OA cartilage and cell samples.
- Knockdown of circSOD2 significantly reduced ECM degradation, inflammation, and apoptosis in the OA cell model.
- circSOD2 knockdown regulated miR-224-5p expression, which in turn downregulated PRDX3 expression.
- The effects of circSOD2 knockdown were reversible with miR-224-5p inhibition or PRDX3 overexpression.
Conclusions:
- circSOD2 plays a crucial role in OA progression.
- Knockdown of circSOD2 demonstrates potential as an intervention strategy for OA.
- The therapeutic effect is mediated through the circSOD2/miR-224-5p/PRDX3 signaling axis.
