title: Effect of inhibiting MMP13 and ADAMTS5 by intra-articular injection of small interfering RNA in a surgically induced osteoarthritis model of mice.
abstract: Matrix metalloproteinase 13 (MMP13) and a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5) are thought to play critical roles in cartilage degradation at the early phase of osteoarthritis (OA). The aim of this study is to examine the effect of chemically modified Mmp13 or Adamts5 small interfering RNA (siRNA), alone or in combination, in a mouse OA model. OA pathology was surgically induced in 9-week-old male C57/BL6 mice (n = 64) via destabilization of the medial meniscus (DMM). We used chemically modified siRNA (Accell siRNAs®) for Mmp13 and Adamts5, as well as a non-targeting control and evaluated their combined and individual effects after injection in the DMM model. The control group (n = 16) was injected with non-targeting siRNA and the normal group (n = 16) did not undergo any surgical induction or intra-articular injection. Histological assessment of the articular cartilage was conducted at 4 and 8 weeks post-DMM surgery to evaluate OA progression. Significant improvement in the histological score was observed at 8 weeks after DMM in all three siRNA-treated groups compared to the control siRNA-injected group. The score of the combined group was significantly lower than that of the Adamts5 siRNA-only group. No significant differences were noted between the Mmp13 siRNA-only group and the combined group. Combined intra-articular injection of Mmp13 and Adamts5 siRNA resulted in almost the same inhibitory effects as Mmp13 siRNA alone on cartilage degradation at the early phase of OA.
authors.affiliation: Department of Orthopedic Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Hoshi
authors.affiliation: Department of Orthopedic Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.
authors.forename: Ryuichiro
authors.initials: R
authors.lastname: Akagi
authors.affiliation: Department of Orthopedic Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamaguchi
authors.affiliation: Department of Orthopedic Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.
authors.forename: Yuta
authors.initials: Y
authors.lastname: Muramatsu
authors.affiliation: Department of Orthopedic Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.
authors.forename: Yorikazu
authors.initials: Y
authors.lastname: Akatsu
authors.affiliation: Department of Orthopedic Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Yamamoto
authors.affiliation: Department of Orthopedic Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.
authors.forename: Toshihide
authors.initials: T
authors.lastname: Sasaki
authors.affiliation: Department of Orthopedic Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: Department of Orthopedic Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan. sasho@faculty.chiba-u.jp.|Center for Preventive Medicine, Chiba University, Chiba, Japan. sasho@faculty.chiba-u.jp.
authors.forename: Takahisa
authors.initials: T
authors.lastname: Sasho
mesh_terms: D000071116:ADAMTS5 Protein / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D004195:Disease Models, Animal; D005453:Fluorescence; D007270:Injections, Intra-Articular; D007596:Joints / Q000473:pathology; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D010003:Osteoarthritis / Q000209:etiology* / Q000473:pathology / Q000628:therapy*; D034741:RNA, Small Interfering / Q000008:administration & dosage*
chemical_list: D034741:RNA, Small Interfering; D000071116:ADAMTS5 Protein; C498489:Adamts5 protein, mouse; D053509:Matrix Metalloproteinase 13
keywords: ADAMTS5; Chemically modified siRNA; Intra-articular injection; MMP13; Mice