Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Evaluation of MiR-181a as a potential therapeutic target in osteoarthritis

Yuqiang Qian^1,2, Jiannong Jiang², Jun Peng², Qiang Wang², Yixin Shen²

¹Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou 215004; ²Department of Orthopedics, The Affiliated Yixing Hospital of Jiangsu University, Yixing 214200, China.

For correspondence:- Yixin Shen Email: shenyixin356@hotmail.com Tel:+8651087921191

Received: 4 January 2017 Accepted: 22 April 2017 Published: 30 May 2017

Citation: Qian Y, Jiang J, Peng J, Wang Q, Shen Y. Evaluation of MiR-181a as a potential therapeutic target in osteoarthritis. Trop J Pharm Res 2017; 16(5):1069-1075 doi: 10.4314/tjpr.v16i5.14

© 2017 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..

Abstract

Purpose: To investigate microRNA-181 (miR-181) as a potential therapeutic target in osteoarthritis (OA).

Methods: MiR-181 expression was evaluated in articular cartilage samples obtained from OA patients undergoing knee arthroplasty and non-OA (control) patients undergoing other orthopedic procedures. Following the isolation of total RNA, miRNA and mRNA expression was determined by real time-polymerase chain reaction (RT-PCR). Luciferase reporter assay and miRNA mimic or inhibitor were then used to establish the molecular target of miR-181 in chondrocytes.

Results: miR-181 family members, namely, miR-181a, miR-181c and miR-181d were significantly up-regulated in articular cartilage obtained from OA patients compared to non-OA control subjects. However, no significant difference in up-regulation of miR-181b expression. B-cell lymphoma 2 (BCL2), a putative target of the miR-181 family, was significantly down-regulated in OA patients compared to control subjects. Furthermore, luciferase reporter assay confirmed direct interaction between miR-181a and three prime untranslated region The 3’UTR of BCL2 in chondrocytes. Transfection of miR-181 mimic resulted in BCL2 suppression in chondrocytes. On the other hand, transfection of miR-181 inhibitor led to increased BCL2 expression and decreased interleukin 1-beta (IL1-β) induced apoptosis.

Conclusion: miR-181 is differentially expressed in articular cartilage of OA patients and leads to down-regulation of BCL2, a regulator of apoptosis. Therefore, miR-181 may be a potential therapeutic target in the treatment of OA

Keywords: MicroRNA, Osteoarthritis, Apoptosis, B-cell lymphoma 2, Transfection, Chondrocytes