BASIC RESEARCH
miR-149-5p mitigates tumor necrosis factor-α-induced chondrocyte apoptosis by inhibiting TRADD
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1
Department of Joint Surgery, the Affiliated Hospital of Jining Medical University, Jining, China
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Department of Orthopedics, the First Affiliated Hospital of Harbin Medical University, Harbin, China
3
Department of Endocrinology, the First Affiliated Hospital of Harbin Medical University, Harbin, China
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Department of Radiology, Tancheng Traditional Chinese Medicine Hospital, Tancheng, China
Submission date: 2019-07-17
Final revision date: 2019-11-26
Acceptance date: 2019-11-27
Online publication date: 2020-01-17
 
 
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ABSTRACT
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.

eISSN:1896-9151
ISSN:1734-1922