Down-regulation of cathepsin K in synovium leads to progression of osteoarthritis in rabbits
Version of Record online: 30 JUL 2009
Copyright © 2009 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 60, Issue 8, pages 2372–2380, August 2009
How to Cite
Takahashi, D., Iwasaki, N., Kon, S., Matsui, Y., Majima, T., Minami, A. and Uede, T. (2009), Down-regulation of cathepsin K in synovium leads to progression of osteoarthritis in rabbits. Arthritis & Rheumatism, 60: 2372–2380. doi: 10.1002/art.24718
- Issue online: 30 JUL 2009
- Version of Record online: 30 JUL 2009
- Manuscript Accepted: 8 MAY 2009
- Manuscript Received: 17 OCT 2008
- Japan Society for the Promotion of Science. Grant Number: Grant-in-Aid for Scientific Research 19591745
The hypothesis of this study was that synovial factors playing a pivotal role in the pathogenesis of osteoarthritis (OA) and thus gene expression in the synovium would be altered at the initial stage of OA. The aims of this study were to identify the candidate genes in synovium related to OA initiation, to evaluate cartilage degeneration after knockdown of the gene using small interfering RNA (siRNA) gene silencing in the knee joints at the initial stage of OA, and to determine the potential role of the knocked-down gene in OA initiation.
Genes overexpressed in synovium at the initial stage of disease in a rabbit model of anterior cruciate ligament transection (ACLT)–induced OA were identified using the suppression subtractive hybridization technique and differential screening. Candidate gene expression in the synovium of the knees of rabbits with OA was manipulated with electroporation-assisted siRNA transduction 4 times before and after operation. Four weeks after surgery, histologic analysis was performed.
Cathepsin K gene and protein expression was significantly up-regulated in synovium at the initial stage of OA in rabbits. Down-regulation of cathepsin K in synovium at the initial stage of OA significantly accelerated cartilage degeneration.
These results indicate that cathepsin K plays a protective role in cartilage degeneration at the initial stage of OA. We believe that the current results obtained from models of the early phase of OA will provide useful information for developing a novel strategy to prevent disease progression.