miR-149-5p mitigates tumor necrosis factor-α-induced chondrocyte apoptosis by inhibiting TRADD

Shi-Cheng Xie; Lin Yang; Taipengfei Shu; Qin Liu; Wenbo Wang

doi:10.5114/aoms.2020.92324

miR-149-5p mitigates tumor necrosis factor-α-induced chondrocyte apoptosis by inhibiting TRADD

Arch Med Sci. 2020 Jan 17;20(2):602-611. doi: 10.5114/aoms.2020.92324. eCollection 2024.

Authors

Shi-Cheng Xie¹, Lin Yang², Taipengfei Shu³, Qin Liu⁴, Wenbo Wang²

Affiliations

¹ Department of Joint Surgery, the Affiliated Hospital of Jining Medical University, Jining, China.
² 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.
⁴ Department of Radiology, Tancheng Traditional Chinese Medicine Hospital, Tancheng, China.

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.

Keywords: TRADD; chondrocyte apoptosis; microRNA; post-transcriptional regulatory mechanism; tumor necrosis factor-α.