Change of miRNA expression profiles in patients with knee osteoarthritis before and after celecoxib treatment

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Abstract

Background

This study aimed to investigate the change of circulating miRNA expression profiles in knee osteoarthritis (OA) patients before and after celecoxib treatment.

Methods

Two hundred and eighteen knee OA patients underwent celecoxib treatment for 6 weeks were enrolled. Plasma samples were obtained at baseline (W0) and at W6, and treatment efficacy were assessed by WOMAC index. In the exploration stage, miRNA expression profiles in plasma before and after treatment from 6 patients were detected by microarray. Subsequently, in the validation stage, 10 top differentially expressed miRNAs (DEMs) after and before treatment in microarray were further validated in all 218 patients by qPCR.

Results

In the exploration stage, patients after treatment could be distinguished from them before treatment by miRNAs expression profiles by PCA plot and heatmap analysis, and 45 up-regulated and 48 down-regulated miRNAs were identified by volcano plot. In the validation stage, miR-126-5p and miR-320a levels increased at W6 compared to W0, while miR-155-5p and miR-146a-5p levels decreased. WOMAC pain/stiffness/physical function scores were all decreased at W6 compared to W0, and 71% of patients achieved clinical response. The increase of miR-126-5p expression (W6-W0) in clinical responders was much larger compared to nonclinical responders. And miRNA-320a level declined in nonclinical responders while increased in clinical responders. Conversely, miRNA-146a-5p level increased in nonclinical responders while decreased in clinical responders.

Conclusion

Circulating miRNA expression profiles act as important roles in knee OA patients underwent celecoxib treatment, and miR-126-5p, miR-320a as well as miR-146a-5p might correlate with treatment response to celecoxib.

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