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Altered microRNA Expression Profile in Synovial Fluid from Patients with Knee Osteoarthritis with Treatment of Hyaluronic Acid

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Abstract

Objective

The aim of this study was to investigate the microRNA (miRNA) expression pattern in synovial fluid from patients with knee osteoarthritis (OA) after treatment with intra-articular injection of hyaluronan (HA).

Methods

Twelve OA patients were enrolled in accordance with the Kellgren–Lawrence classification of knee OA. All patients received intra-articular injection of HA once a week for 5 weeks and were evaluated with the Western Ontario and McMaster Universities (WOMAC) index at baseline. TaqMan miRNA assay profiling was performed on synovial fluid RNAs extracted from OA patients pre-injection and after 5 weeks of treatment with HA. Validation was performed using independent samples, including ten healthy controls and ten matched OA patients.

Results

Forty-three miRNAs (21 overexpressed miRNAs and 22 underexpressed miRNAs) were differentially expressed in OA patients before and after treatment with HA (P < 0.05, false discovery rate corrected). Further bioinformatics prediction by mirPath indicated that the differential miRNA signatures in synovial fluid extracted from the OA patients demonstrated primarily upregulation of the PI3K-Akt signaling pathway, mitogen-activated protein kinase signaling pathway, regulation of autophagy, mRNA surveillance pathway, and B cell receptor signaling pathway. In addition, TaqMan real-time reverse transcription polymerase chain reaction was performed for validation on miR-146a, miR-155, let-7a, miR-181a, miR-454, and let-7b, which were significantly changed in abundance, using an independent cohort of ten healthy controls and ten OA patients as compared with those with intra-articular injection of HA.

Conclusion

Our results demonstrated that dysregulation in miRNAs in synovial fluid from OA patients and their affected biologic cellular processes might play important role in OA pathogenesis and HA-mediated therapeutics.

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Acknowledgments

The authors thank all of the patients who participated in this study and the staff from the Department of Orthopedics, Zhejiang Provincial People’s Hospital, Hangzhou, PR China.

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Authors and Affiliations

  1. Department of Orthopedics and Joint Surgery, Zhejiang Provincial People’s Hospital, Hangzhou, 310014, People’s Republic of China

    Ji-Feng Xu, Shui-Jun Zhang, Chen Zhao, Bin-Song Qiu, Hai-Feng Gu, Jian-Fei Hong, Li Cao, Yu Chen, Bing Xia & Qin Bi

  2. Department of Cardiology, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310009, People’s Republic of China

    Ya-Ping Wang

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  1. Ji-Feng Xu
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Correspondence to Ji-Feng Xu or Ya-Ping Wang.

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None of the authors have any financial relationships to report.

Funding

This study was supported by the Medical Scientific Research Foundation of Zhejiang Province, China (grant no. 2013KYB031) (Y. P. W, J. F. X), the National Natural Science Foundation of China (grant no. 81200113) (Y. P. W, J. F. X), the Fundamental Research Funds for the Central Universities (grant no. 2014FZA7014) (Y. P. W, J. F. X), the Natural Science Foundation of Zhejiang Province, China (grant no. LQ15H060003) (Y. P. W, J. F. X), and the Natural Science Foundation of Zhejiang Province, China (grant no. LY15H020005) (Y. P. W, J. F. X).

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Xu, JF., Zhang, SJ., Zhao, C. et al. Altered microRNA Expression Profile in Synovial Fluid from Patients with Knee Osteoarthritis with Treatment of Hyaluronic Acid. Mol Diagn Ther 19, 299–308 (2015). https://doi.org/10.1007/s40291-015-0155-2

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