title: Adiponectin increases MMP-3 expression in human chondrocytes through AdipoR1 signaling pathway.
abstract: Articular adipose tissue is a ubiquitous component of human joints, and adiponectin is a protein hormone secreted predominantly by differentiated adipocytes and involved in energy homeostasis. The adiponectin is significantly higher in synovial fluid of patients with osteoarthritis and rheumatoid arthritis. Matrix metalloproteinases (MMP)-3 may contribute to the breakdown of articular cartilage during arthritis. We investigated the signaling pathway involved in MMP-3 caused by adiponectin in human chondrocytes. Adiponectin increased the secretion of MMP-3 in cultured human chondrocytes, as shown by qPCR, Western blot, and ELISA analysis. Adiponectin-mediated MMP-3 expression was attenuated by AdipoR1 but not AdipoR2 siRNA. Pretreatment with 5'-AMP-activated protein kinase (AMPK) inhibitor (araA and compound C), p38 inhibitor (SB203580), and NF-κB inhibitor (PDTC and TPCK) also inhibited the potentiating action of adiponectin. Activations of p38, AMPK, and NF-κB pathways after adiponectin treatment were demonstrated. Taken together, our results provide evidence that adiponectin acts through AdipoR1 to activate p38 and AMPK, resulting in the activations of NF-κB on the MMP-3 promoter and contribute cartilage destruction during arthritis.
authors.affiliation: Department of Orthopaedics, Taichung Veterans General Hospital, Taichung, Taiwan.
authors.forename: Kwok-Man
authors.initials: KM
authors.lastname: Tong
authors.forename: Chao-Ping
authors.initials: CP
authors.lastname: Chen
authors.forename: Kui-Chou
authors.initials: KC
authors.lastname: Huang
authors.forename: Dong-Chen
authors.initials: DC
authors.lastname: Shieh
authors.forename: Hsu-Chen
authors.initials: HC
authors.lastname: Cheng
authors.forename: Chung-Yuh
authors.initials: CY
authors.lastname: Tzeng
authors.forename: Kun-Hui
authors.initials: KH
authors.lastname: Chen
authors.forename: Yung-Cheng
authors.initials: YC
authors.lastname: Chiu
authors.forename: Chih-Hsin
authors.initials: CH
authors.lastname: Tang
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D052242:Adiponectin / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000273:Adipose Tissue / Q000378:metabolism; D019902:Chondrocytes / Q000201:enzymology* / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D019278:Matrix Metalloproteinase 3 / Q000096:biosynthesis* / Q000235:genetics; D016328:NF-kappa B / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D054419:Receptors, Adiponectin / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013582:Synovial Fluid / Q000201:enzymology / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: C475418:ADIPOR1 protein, human; C475420:ADIPOR2 protein, human; D052242:Adiponectin; D016328:NF-kappa B; D034741:RNA, Small Interfering; D054419:Receptors, Adiponectin; D011494:Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D000091162:AMP-Activated Protein Kinase Kinases; D019278:Matrix Metalloproteinase 3