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Published on: January 7, 2019
miR-149-5p mitigates tumor necrosis factor-α-induced chondrocyte apoptosis by inhibiting TRADD
Shi-Cheng Xie1, Lin Yang2, Taipengfei Shu3
1Department of Joint Surgery, the Affiliated Hospital of Jining Medical University, Jining, China.
Introduction:
Chondrocyte apoptosis as a prominent characteristic is usually accompanied by cartilage degeneration in osteoarthritis (OA). Herein, we aimed to determine the roles of miR-149-5p in tumor necrosis factor-α (TNF-α)-induced chondrocyte apoptosis.
Material And Methods:
Human chondrocytes were cultured with TNF-α to establish an apoptosis cell model in vitro. After transfection with miR-149-5p mimics or co-expression with TRADD in chondrocytes, cell viability, apoptosis, inflammatory cytokines, mRNA and protein expression were measured using CCK8, Annexin V-FITC double staining, ELISA assays, RT-qPCR and western blotting, respectively.
Results:
TNF-α-induced chondrocyte apoptosis occurred in association with the inhibition of cell proliferation, the elevation of inflammatory cytokine levels and the activation of TRADD and caspase-3/8 signaling. The post-transcriptional regulatory mechanism suggested that TRADD was a direct target of miR-149-5p, and overexpression of miR-149-5p resulted in the down-regulation of TRADD protein expression in chondrocytes. In addition, miR-149-5p mimics had the ability to attenuate TNF-α-induced inflammation and apoptosis, while transfection with TRADD vector neutralized the protective effects of miR-149-5p on TNF-α-induced chondrocyte dysfunction.
Conclusions:
miR-149-5p inversely regulated TNF-α-mediated chondrocyte damage by inhibiting TRADD-modulated caspases signaling. The miR-149-5p/TRADD signaling pathway might be a promising therapeutic target for the treatment of OA.
Insights
MicroRNA-149-5p protects against osteoarthritis by inhibiting TRADD-modulated caspase signaling, reducing chondrocyte apoptosis and inflammation. This pathway offers a potential therapeutic target for treating osteoarthritis.
Area of Science:
- Biochemistry
- Molecular Biology
- Cell Biology
Background:
- Osteoarthritis (OA) is characterized by chondrocyte apoptosis and cartilage degeneration.
- Tumor necrosis factor-alpha (TNF-α) plays a significant role in inducing chondrocyte apoptosis in OA.
Purpose of the Study:
- To investigate the role of microRNA-149-5p (miR-149-5p) in TNF-α-induced chondrocyte apoptosis.
- To elucidate the underlying molecular mechanisms involving TRADD and caspase signaling.
Main Methods:
- Establishment of an in vitro chondrocyte apoptosis model using TNF-α.
- Transfection with miR-149-5p mimics or TRADD expression vectors.
- Assessment of cell viability, apoptosis, inflammatory cytokines, and protein/mRNA expression via CCK8, Annexin V-FITC, ELISA, RT-qPCR, and Western blotting.
Main Results:
- TNF-α induced chondrocyte apoptosis, inflammation, and activated TRADD and caspase-3/8 signaling.
- TRADD was identified as a direct target of miR-149-5p, with miR-149-5p overexpression down-regulating TRADD.
- miR-149-5p mimics attenuated TNF-α-induced apoptosis and inflammation, while TRADD overexpression counteracted these protective effects.
Conclusions:
- miR-149-5p inhibits TNF-α-mediated chondrocyte damage by down-regulating TRADD and modulating caspase signaling.
- The miR-149-5p/TRADD pathway presents a potential therapeutic target for osteoarthritis treatment.
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