title: Adiponectin enhances intercellular adhesion molecule-1 expression and promotes monocyte adhesion in human synovial fibroblasts.
abstract: Adiponectin is a protein hormone secreted predominantly by differentiated adipocytes and is involved in energy homeostasis. Adiponectin expression is significantly high in the synovial fluid of patients with osteoarthritis (OA). Intercellular adhesion molecule-1 (ICAM-1) is an important adhesion molecule that mediates monocyte adhesion and infiltration during OA pathogenesis. Adiponectin-induced expression of ICAM-1 in human OA synovial fibroblasts (OASFs) was examined by using qPCR, flow cytometry and western blotting. The intracellular signaling pathways were investigated by pretreated with inhibitors or transfection with siRNA. The monocyte THP-1 cell line was used for an adhesion assay with OASFs. Stimulation of OASFs with adiponectin induced ICAM-1 expression. Pretreatment with AMP-activated protein kinase (AMPK) inhibitors (AraA and compound C) or transfection with siRNA against AMPKα1 and two AMPK upstream activator- liver kinase B1 (LKB1) and calmodulin-dependent protein kinase II (CaMKII) diminished the adiponectin-induced ICAM-1 expression. Stimulation of OASFs with adiponectin increased phosphorylation of LKB1, CaMKII, AMPK, and c-Jun, resulting in c-Jun binding to AP-1 element of ICAM-1 promoter. In addition, adiponectin-induced activation of the LKB1/CaMKII, AMPK, and AP-1 pathway increased the adhesion of monocytes to the OASF monolayer. Our results suggest that adiponectin increases ICAM-1 expression in human OASFs via the LKB1/CaMKII, AMPK, c-Jun, and AP-1 signaling pathway. Adiponectin-induced ICAM-1 expression promoted the adhesion of monocytes to human OASFs. These findings may provide a better understanding of the pathogenesis of OA and can utilize this knowledge to design a new therapeutic strategy.
authors.affiliation: School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan; Department of Orthopaedic Surgery, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Hsien-Te
authors.initials: HT
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, Taichung Veterans General Hospital, Taichung, Taiwan; Department of Early Childhood Care and Education, Jen-Teh Junior College of Medicine, Nursing and Management, Miaoli County, Taiwan.
authors.forename: Hsi-Kai
authors.initials: HK
authors.lastname: Tsou
authors.affiliation: Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan; National Institute of Cancer Research, National Health Research Institutes, Miaoli County, Zhunan, Taiwan.
authors.forename: Jui-Chieh
authors.initials: JC
authors.lastname: Chen
authors.affiliation: Department of Orthopaedic Surgery, Lin Sen Hospital, Taichung, Taiwan.
authors.forename: James Meng-Kun
authors.initials: JM
authors.lastname: Shih
authors.affiliation: Department of Orthopaedic Surgery, China Medical University Hospital, Taichung, Taiwan; School of Medicine, China Medical University, Taichung, Taiwan.
authors.forename: Yen-Jen
authors.initials: YJ
authors.lastname: Chen
authors.affiliation: School of Medicine, China Medical University, Taichung, Taiwan; Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan; Department of Biotechnology, College of Health Science, Asia University, Taichung, Taiwan.
authors.forename: Chih-Hsin
authors.initials: CH
authors.lastname: Tang
mesh_terms: D052242:Adiponectin / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D005260:Female; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*; D008297:Male; D009000:Monocytes / Q000378:metabolism* / Q000473:pathology; D010003:Osteoarthritis / Q000378:metabolism / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011494:Protein Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013583:Synovial Membrane / Q000378:metabolism* / Q000473:pathology
chemical_list: C499918:ADIPOQ protein, human; D052242:Adiponectin; D047428:Protein Kinase Inhibitors; D018799:Intercellular Adhesion Molecule-1; D011494:Protein Kinases