Adiponectin increases MMP-3 expression in human chondrocytes through AdipoR1 signaling pathway

Department of Orthopaedics, Taichung Veterans General Hospital, Taichung, Taiwan.
Journal of Cellular Biochemistry (Impact Factor: 3.26). 05/2011; 112(5):1431-40. DOI: 10.1002/jcb.23059
Source: PubMed


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.

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Available from: Yung Cheng Chiu,
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    • "However, evidence that adiponectin may act as a proinflammatory mediator promoting extracellular matrix degradation and joint disruption is also available. Indeed, in cultured chondrocytes, adiponectin increases the expression of MMP-3 [21] and the secretion and activity of proinflammatory mediators, such as nitric oxide synthase type II (NOS2/iNOS), MMP-9, IL-6, MCP-1, and IL-8 [22, 23]. Similarly, adiponectin is able to stimulate the production of PGE2, IL-6, IL-8, vascular endothelial growth factor (VEGF), MMP-1 and MMP-13, cyclooxygenase 2 (COX-2), and microsomal prostaglandin E synthase 1 (mPGES-1) [24, 25] in RA synovial fibroblasts (Figure 1). "
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    • "In contrast to its previously described protective role in CVDs and obesity, there are multiple lines of evidence that adiponectin acts as a proinflammatory factor in joints and it could be involved in matrix degradation. In cultured chondrocytes, adiponectin stimulates the secretion of proinflammatory mediators (iNOS, IL-6, and IL-8) [75, 101] and increases MMP-3 expression [102]. Adiponectin levels have been found to be higher in RA patients than in healthy controls [57, 63, 67, 103, 104]. "
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