Effective knock down of matrix metalloproteinase‐13 by an intra‐articular injection of small interfering RNA (siRNA) in a murine surgically‐induced osteoarthritis model. Issue 9 (22nd May 2014)

• Record Type: Journal Article
• Authors: Akagi, Ryuichiro; Sasho, Takahisa; Saito, Masahiko; Endo, Jun; Yamaguchi, Satoshi; Muramatsu, Yuta; Mukoyama, Shunsuke; Akatsu, Yorikazu; Katsuragi, Joe; Fukawa, Taisuke; Takahashi, Kazuhisa
• Is Part Of: Journal of orthopaedic research. Volume 32:Issue 9(2014:Sep.)
• Page Start: 1175
• Page End: 1180
• Publication Date: 2014-05-22
• Subjects: Orthopedics -- Periodicals; Musculoskeletal system -- Periodicals; 616.7
• DOI: 10.1002/jor.22654
• Languages: English
• ISSNs: 0736-0266

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>ABSTRACT</title> <sec id="jor22654-sec-0001" sec-type="section"> <p>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 <italic>Mmp13</italic> expression over time was determined by qPCR analysis from 3 days to 6 weeks after surgery. <italic>Mmp13</italic> 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. <italic>Mmp13</italic> 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 <italic>Mmp13</italic> levels in cartilage was observed 48 h after injection of <italic>Mmp13</italic> siRNA (<italic>p</italic> = 0.05). Significant reduction in the histological score at 8 weeks after surgery was observed in the <italic>Mmp13</italic> siRNA‐treated group compared to the control siRNA group (<italic>p</italic> < 0.001). Intra‐articular injection of <italic>Mmp13</italic> siRNA at the early phase of OA development resulted in effective knock down of <italic>Mmp13</italic> expression and delay in cartilage degradation in vivo. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:1175–1180, 2014.</p> </sec> </abstract>