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Published on: March 18, 2022
CircFNDC3B regulates osteoarthritis and oxidative stress by targeting miR-525-5p/HO-1 axis
Zizheng Chen1,2,3, Yizhen Huang1,2,3, Yu Chen1,3
1Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 3 East Qingchun Road, Hangzhou, 310016, Zhejiang Province, China.
Abstract:
Osteoarthritis (OA) is a common chronic degenerative joint disease associated with a variety of risk factors including aging, genetics, obesity, and mechanical disturbance. This study aimed to elucidate the function of a newly discovered circular RNA (circRNA), circFNDC3B, in OA progression and its relationship with the NF-κB signaling pathway and oxidative stress. The circFNDC3B/miR-525-5p/HO-1 axis and its relationship with the NF-κB signaling pathway and oxidative stress were investigated and validated using fluorescence in situ hybridization, real-time PCR, western blotting, immunofluorescence analysis, luciferase reporter assays, pull-down assays, and reactive oxygen species analyses. The functions of circFNDC3B in OA was investigated in vitro and in vivo. These evaluations demonstrated that circFNDC3B promotes chondrocyte proliferation and protects the extracellular matrix (ECM) from degradation. We also revealed that circFNDC3B defends against oxidative stress in OA by regulating the circFNDC3B/miR-525-5p/HO-1 axis and the NF-κB signaling pathway. Further, we found that overexpression of circFNDC3B alleviated OA in a rabbit model. In summary, we identified a new circFNDC3B/miR-525-5p/HO-1 signaling pathway that may act to relieve OA by alleviating oxidative stress and regulating the NF-κB pathway, resulting in the protection of the ECM in human chondrocytes, highlighting it as a potential therapeutic target for the treatment of OA.
Insights
A newly discovered circular RNA, circFNDC3B, was found to protect against osteoarthritis (OA) by reducing oxidative stress and regulating key signaling pathways. This finding highlights circFNDC3B as a potential therapeutic target for OA treatment.
Area of Science:
- Molecular Biology
- Biochemistry
- Cell Biology
Background:
- Osteoarthritis (OA) is a prevalent degenerative joint disease influenced by aging, genetics, obesity, and mechanical stress.
- Understanding the molecular mechanisms underlying OA progression is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the role of the novel circular RNA, circFNDC3B, in osteoarthritis.
- To elucidate the relationship between circFNDC3B, the NF-κB signaling pathway, and oxidative stress in OA.
- To explore the therapeutic potential of circFNDC3B in OA treatment.
Main Methods:
- In vitro and in vivo experiments using human chondrocytes and a rabbit OA model.
- Techniques included fluorescence in situ hybridization, real-time PCR, western blotting, immunofluorescence, luciferase reporter assays, pull-down assays, and reactive oxygen species analysis.
- Investigation of the circFNDC3B/miR-525-5p/HO-1 axis and its impact on NF-κB signaling and oxidative stress.
Main Results:
- circFNDC3B was found to promote chondrocyte proliferation and protect the extracellular matrix (ECM) from degradation.
- circFNDC3B alleviates oxidative stress in OA by modulating the circFNDC3B/miR-525-5p/HO-1 axis and the NF-κB signaling pathway.
- Overexpression of circFNDC3B demonstrated a therapeutic effect in a rabbit model of OA.
Conclusions:
- A novel circFNDC3B/miR-525-5p/HO-1 signaling pathway was identified in osteoarthritis.
- This pathway alleviates OA by reducing oxidative stress and regulating the NF-κB pathway, thereby protecting the extracellular matrix.
- circFNDC3B represents a promising therapeutic target for osteoarthritis treatment.
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