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Adiponectin increases MMP‐3 expression in human chondrocytes through adipor1 signaling pathway
Author(s) -
Tong KwokMan,
Chen ChaoPing,
Huang KuiChou,
Shieh DongChen,
Cheng HsuChen,
Tzeng ChungYuh,
Chen KunHui,
Chiu YungCheng,
Tang ChihHsin
Publication year - 2011
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.23059
Subject(s) - adiponectin , ampk , matrix metalloproteinase , p38 mitogen activated protein kinases , endocrinology , adiponectin receptor 1 , adipokine , medicine , adipose tissue , protein kinase a , signal transduction , chemistry , western blot , microbiology and biotechnology , kinase , biology , leptin , insulin resistance , biochemistry , insulin , obesity , gene
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. J. Cell. Biochem. 112: 1431–1440, 2011. © 2011 Wiley‐Liss, Inc.