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- Title
Effective knock down of matrix metalloproteinase-13 by an intra-articular injection of small interfering RNA (siRNA) in a murine surgically-induced osteoarthritis model.
- Authors
Akagi, Ryuichiro; Sasho, Takahisa; Saito, Masahiko; Endo, Jun; Yamaguchi, Satoshi; Muramatsu, Yuta; Mukoyama, Shunsuke; Akatsu, Yorikazu; Katsuragi, Joe; Fukawa, Taisuke; Takahashi, Kazuhisa
- Abstract
ABSTRACT This study investigated the effect of MMP-13 gene knock down on cartilage degradation by injecting small interfering RNA (siRNA) into knee joints in a mouse model of osteoarthritis (OA). OA was induced in male C57BL/6 mice by destabilization of medial meniscus (DMM) surgery. Change of Mmp13 expression over time was determined by qPCR analysis from 3 days to 6 weeks after surgery. Mmp13 and control chemically modified siRNA were injected into the knee joint 1 week after surgery and expression levels were assessed in synovium by qPCR 48 h later. Cartilage degradation was histologically assessed 8 weeks after DMM surgery according to OARSI recommendations. Mmp13 expression levels were elevated 1 week after surgery and peaked at 77 fold at 2 weeks compared to expression at 3 days. A 55% decrease of Mmp13 levels in cartilage was observed 48 h after injection of Mmp13 siRNA ( p = 0.05). Significant reduction in the histological score at 8 weeks after surgery was observed in the Mmp13 siRNA-treated group compared to the control siRNA group ( p < 0.001). Intra-articular injection of Mmp13 siRNA at the early phase of OA development resulted in effective knock down of Mmp13 expression and delay in cartilage degradation in vivo. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:1175-1180, 2014.
- Subjects
MATRIX metalloproteinases; SMALL interfering RNA; OSTEOARTHRITIS; GENE knockout; CARTILAGE; MENISCUS surgery; RNA interference; ANIMAL models in research
- Publication
Journal of Orthopaedic Research, 2014, Vol 32, Issue 9, p1175
- ISSN
0736-0266
- Publication type
Article
- DOI
10.1002/jor.22654