Department of Orthopaedics, Taichung Veterans General Hospital, Taichung, Taiwan.
J Cell Biochem. 2011 May;112(5):1431-40. doi: 10.1002/jcb.23059.
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.
关节内脂肪组织是人类关节的一种普遍组成部分，脂联素是一种主要由分化的脂肪细胞分泌的蛋白激素，参与能量平衡。在骨关节炎和类风湿关节炎患者的滑液中，脂联素明显更高。基质金属蛋白酶（MMP）-3 可能有助于关节炎期间关节软骨的破坏。我们研究了脂联素在人软骨细胞中引起 MMP-3 的信号通路。脂联素通过 qPCR、Western blot 和 ELISA 分析增加了培养的人软骨细胞中 MMP-3 的分泌。脂联素介导的 MMP-3 表达被 AdipoR1 但不是 AdipoR2 siRNA 减弱。用 5'-AMP 激活的蛋白激酶（AMPK）抑制剂（araA 和化合物 C）、p38 抑制剂（SB203580）和 NF-κB 抑制剂（PDTC 和 TPCK）预处理也抑制了脂联素的增强作用。在用脂联素处理后，p38、AMPK 和 NF-κB 途径的激活得到了证明。总之，我们的结果提供了证据，表明脂联素通过 AdipoR1 激活 p38 和 AMPK，导致 MMP-3 启动子上 NF-κB 的激活，并有助于关节炎期间软骨的破坏。
