title: Chondroprotective effects and multi-target mechanisms of Icariin in IL-1 beta-induced human SW 1353 chondrosarcoma cells and a rat osteoarthritis model.
abstract: Cartilage degradation is the most predominant pathological change during osteoarthritis (OA). Furthermore, accumulating evidence suggests that an excess of matrix metalloproteinase-13 (MMP-13) plays a critical role in the breakdown of cartilage. Here, the effects of Icariin on the expression of MMP-13 in IL-1β-induced SW 1353 chondrosarcoma cells were investigated. In addition, the in vivo effects of Icariin on an experimental rat model of OA induced by anterior cruciate ligament transection (ACLT) was examined. SW1353 chondrosarcoma cells were pretreated with or without Icariin and MAPK and Wnt/β-catenin signaling pathway inhibitors, then were stimulated with IL-1β. In rats, experimental OA was induced by ACLT. These rats then received intra-articular injections of vehicle, signaling pathway inhibitors, and/or Icariin. Expression of MMP-13, phosphorylated p38, phosphorylated JNK, and β-catenin were verified by western blotting. In addition, levels of MMP-13 mRNA were detected using quantitative real-time PCR. In histological analyses, treatment with Icariin reduced the number of cartilage lesions present. In addition, treatment with Icariin was associated with lower levels of phosphorylated p38, phosphorylated JNK, and β-catenin in both IL-1β-induced SW1353 chondrosarcoma cells and in the rat OA model. Furthermore, the suppressive effect of Icariin on MMP-13 was greater than that exhibited by other signaling pathway inhibitors. Overall, these data suggest that Icariin has therapeutic potential for the treatment of OA.
authors.affiliation: Department of Combination of Chinese and Western Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, PR China; Laboratory Research Center, 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; 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: 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.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhong
authors.affiliation: Department of Combination of Chinese and Western Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, PR China.
authors.forename: Ping
authors.initials: P
authors.lastname: Jia
authors.affiliation: Department of Combination of Chinese and Western Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, PR China.
authors.forename: Guo-Qing
authors.initials: GQ
authors.lastname: Zhou
authors.affiliation: Department of Combination of Chinese and Western Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, PR China. Electronic address: baihe_han@126.com.
authors.forename: Rong-Heng
authors.initials: RH
authors.lastname: Li
mesh_terms: D000818:Animals; D016118:Anterior Cruciate Ligament / Q000601:surgery; D002356:Cartilage / Q000187:drug effects* / Q000473:pathology; D045744:Cell Line, Tumor; D002813:Chondrosarcoma / Q000188:drug therapy* / Q000276:immunology; D004195:Disease Models, Animal; D005419:Flavonoids / Q000008:administration & dosage* / Q000009:adverse effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007375:Interleukin-1 / Q000276:immunology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D053509:Matrix Metalloproteinase 13 / Q000235:genetics / Q000378:metabolism*; D010003:Osteoarthritis / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D051153:Wnt Proteins / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
chemical_list: D005419:Flavonoids; D007375:Interleukin-1; D051153:Wnt Proteins; D051176:beta Catenin; C437372:interleukin-1 delta; D053509:Matrix Metalloproteinase 13; C056599:icariin
keywords: Icariin; JNK; Matrix metalloproteinase-13; Osteoarthritis; p38; β-catenin