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ISSN: 2167-7921

Journal of Arthritis
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Research Article

In Vitro and in Silico Analysis of ADAMTS5 Transcription in Human Chondrocytes

Kazunori Hamamura1*, Andy Chen1, Nancy Tanjung1, Hui B Sun2 and Hiroki Yokota1,3
1Department of Biomedical Engineering, Indiana University- Purdue University Indianapolis, Indianapolis, IN 46202, USA
2Department of Orthopaedic Surgery, Albert Einstein College of Medicine, Bronx, NY 10461, USA
3Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
Corresponding Author : Kazunori Hamamura
Department of Biomedical Engineering
Indiana University-Purdue University Indianapolis
723 West Michigan Street, Indianapolis, IN 46202 USA
Tel: (317) 278-5177
Fax: (317) 278-2455
E-mail: [email protected]
Received September 16, 2013; Accepted October 16, 2013; Published October 23, 2013
Citation: Hamamura K, Chen A, Tanjung N, Sun HB, Yokota H (2013) In Vitro and in Silico Analysis of ADAMTS5 Transcription in Human Chondrocytes. J Arthritis 2:111. doi:10.4172/2167-7921.1000111
Copyright: © 2013 Hamamura K, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Osteoarthritis is a major cause of disability in the adult population. Exercise is commonly prescribed, but the mechanisms underlying mechanotransduction of joint tissues are not well understood. Since Lrp5 is an important mechano-sensitive receptor in Wnt signaling, we examined its role in the mRNA expression of A Disintegrin and Metalloproteinase with Thrombospondin Motifs 5 (ADAMTS5), a major proteolytic aggrecanase that degrades extracellular matrix in articular cartilage. Using genome-wide expression data for C28/I2 chondrocytes with and without Lrp5-specific siRNA, we employed a systems biology approach and built a regulatory network model. Experimental data revealed that silencing Lrp5 significantly altered Wnt signaling gene expression and elevated the mRNA level of ADAMTS5 and several cytokines. A series of experiments using RNA interference showed that the expression of ADAMTS5 was at least in part stimulated by p38 MAPK and IL1β, while Lrp5 acted as a suppressor of their upregulation. Regulatory network analysis using an algorithm predicted the potential involvement of Wnt3a, Myc and CCAAT/Enhancer-Binding Protein β (CEBPB). Collectively, the systems biology approach helped develop an Lrp5-mediated network model in regulation of ADAMTS5, and the model predicted that a secretary factor such as Wnt3a might be involved in Lrp5-mediated homeostasis of ADAMTS5.

Keywords

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