title: Ginsenoside Rb1 inhibits matrix metalloproteinase 13 through down-regulating Notch signaling pathway in osteoarthritis.
abstract: Mounting evidence suggests that an excess of matrix metalloproteinase-13 (MMP-13) plays an important role in the breakdown of extracellular matrix in osteoarthritis (OA). Here, the effects of ginsenoside Rb1 (GRb1) on the expression of MMP-13 in IL-1β-induced SW 1353 chondrosarcoma cells and an experimental rat model of OA induced by anterior cruciate ligament transection (ACLT) were investigated. SW1353 chondrosarcoma cells were pretreated with or without GRb1 and Notch signaling pathway inhibitor, DAPT, then were stimulated with IL-1β. In rats, experimental OA was induced by ACLT. These rats then received intra-articular injections of vehicle, an inhibitor of γ-secretase, DAPT, and/or GRb1. Expression of MMP-13, collagen type II (CII), Notch1, and jagged 1 (JAG1) were verified by western blotting and immunohistochemistry. In addition, levels of MMP-13 mRNA were detected using quantitative real-time PCR. In histological analyses, treatment with DAPT reduced the number of cartilage lesions present and the expressions of MMP-13, CII, Notch1, and JAG1. In addition, treatment with GRb1 was associated with lower levels of Notch1 and JAG1 in both IL-1β-induced SW1353 chondrosarcoma cells and in the rat OA model. Furthermore, the suppressive effect of GRb1 on MMP-13 was greater than that exhibited by the signaling pathway inhibitor. In conclusion, GRb1 inhibits MMP-13 through down-regulating Notch signaling pathway in OA.
authors.affiliation: Department of Combination of Chinese and Western Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, PR China Department of Traditional Chinese Medicine for Tumor, Chongqing Cancer Institute, Chongqing 400030, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Combination of Chinese and Western Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Zeng
authors.affiliation: Department of Combination of Chinese and Western Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, PR China.
authors.forename: Ze-ming
authors.initials: ZM
authors.lastname: Wang
authors.affiliation: Department of Combination of Chinese and Western Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, PR China.
authors.forename: Sihan
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Combination of Chinese and Western Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, PR China.
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Rong
authors.affiliation: Department of Combination of Chinese and Western Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, PR China baihe_han@yeah.net.
authors.forename: Rong-Heng
authors.initials: RH
authors.lastname: Li
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001859:Bone Neoplasms / Q000503:physiopathology; D045744:Cell Line, Tumor; D002813:Chondrosarcoma / Q000503:physiopathology; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects; D036145:Ginsenosides / Q000494:pharmacology*; D053509:Matrix Metalloproteinase 13 / Q000187:drug effects / Q000502:physiology*; D061965:Matrix Metalloproteinase Inhibitors / Q000494:pharmacology*; D010003:Osteoarthritis / Q000188:drug therapy / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D051880:Receptors, Notch / Q000187:drug effects / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology
chemical_list: D036145:Ginsenosides; D061965:Matrix Metalloproteinase Inhibitors; D051880:Receptors, Notch; C442759:ginsenoside Rb1; D053509:Matrix Metalloproteinase 13
keywords: Matrix metalloproteinase-13; ginsenoside Rb1; notch signaling pathway; osteoarthritis