Overexpression of miR-150 alleviates mechanical stress-accelerated the apoptosis of chondrocytes via targeting GRP94

Z.-Q. Zhang, C.-S. Wang, P. Yang, K.-Z. Wang

Department of Orthopedic Surgery, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, P.R. China. wang_kkzz@sina.com

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• Orthopedics

OBJECTIVE: A previous study reported that glucose-regulated protein 94 (GRP94) is involved in mechanical stress-induced chondrocyte apoptosis; however, the underlying molecular mechanisms remain unknown. The present study aimed to investigate the post-transcriptional regulatory mechanism of microRNAs (miRs) in mechanical stress-induced chondrocyte apoptosis by targeting GRP94.
MATERIALS AND METHODS: Annexin V-fluorescein isothiocyanate/propidium iodide (PI) staining was conducted to evaluate the apoptosis of chondrocytes. The mRNA and protein expression levels were measured by reverse transcription-quantitative polymerase chain reaction and Western blotting, respectively. The targeted genes were predicted using a bioinformatics tool and further investigated via a luciferase reporter assay.
RESULTS: The results demonstrated that cyclic loading led to significant increases in GRP94 expression in chondrocytes; however, the expression levels of miR-150 were downregulated. Bioinformatics analysis and a luciferase reporter assay indicated that GRP94 was a direct target of miR-150, as the expression of GRP94 was dysregulated following transfection with miR-150 mimics or inhibitors. In addition, mechanical stress-induced chondrocyte apoptosis was suppressed by transfection with miR-150 mimics, while the protective effects of miR-150 mimics in this process were inhibited by GRP94 overexpression.
CONCLUSIONS: MiR-150 upregulation suppressed mechanical stress-induced chondrocyte apoptosis; the underlying molecular mechanism may be mediated, at least partially, via the inhibition of GRP94 expression.

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