Effective knock down of matrix metalloproteinase-13 by an intra-articular injection of small interfering RNA (siRNA) in a murine surgically-induced osteoarthritis model.
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.
Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana Chuo-ku, Chiba, Chiba, 260-8670, Japan.
Ryuichiro
R
Akagi
Takahisa
T
Sasho
Masahiko
M
Saito
Jun
J
Endo
Satoshi
S
Yamaguchi
Yuta
Y
Muramatsu
Shunsuke
S
Mukoyama
Yorikazu
Y
Akatsu
Joe
J
Katsuragi
Taisuke
T
Fukawa
Kazuhisa
K
Takahashi
D000818:Animals; D004195:Disease Models, Animal; D055785:Gene Knockdown Techniques; D007270:Injections, Intra-Articular; D007719:Knee Joint / Q000187:drug effects / Q000473:pathology; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000187:drug effects* / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D020370:Osteoarthritis, Knee / Q000188:drug therapy* / Q000473:pathology; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000494:pharmacology*; D012720:Severity of Illness Index; D016896:Treatment Outcome
D034741:RNA, Small Interfering; D053509:Matrix Metalloproteinase 13
DMM; MMP-13; in vivo; mouse; siRNA