Department of Orthopedic Surgery, The Second Hospital of Medical College, Zhejiang University College of Medicine, Hangzhou, PR China.
Int J Mol Med. 2010 Sep;26(3):357-63.
Adipokines play key roles in the regulation of bone growth, obesity, diabetes mellitus type 2, and HIV infection. As a newly discovered hormone in the adipokine family, the precise role of apelin on articular cartilage metabolism is not yet clear. The aim of this study was to evaluate the role of apelin on articular cartilage. In vitro, we examined the effects of apelin on normal chondrocyte proliferation and gene expression of metalloproteinases (MMPs) and interleukin-1beta (IL-1beta). In vivo, by intra-articular injection with apelin, we examined MMP-3, -9, collagen II and IL-1beta at both gene and protein levels. Furthermore, we measured the messenger RNA (mRNA) expression of ADAMTS-4 and -5 (a disintegrin and metalloproteinase with thrombospondin motifs 4 and 5) and the proteoglycan content in articular cartilage. Apelin stimulated the proliferation of chondrocytes and significantly increased mRNA levels of MMP-1, -3, -9 and IL-1beta in vitro. Intra-articular injection with apelin in vivo up-regulated the expression of MMP-3, -9, and IL-1beta as well as decreased the level of collagen II. Additionally, after treatment with apelin, mRNA levels of ADAMTS-4 and -5 markedly increased and depletion of proteoglycan in articular cartilage was found by histological assessment. These findings suggest that apelin plays a catabolic role in cartilage metabolism and is a risk factor in the pathophysiology of osteoarthritis.
脂肪细胞因子在骨骼生长、肥胖、2 型糖尿病和 HIV 感染的调节中发挥关键作用。作为脂肪细胞因子家族中一种新发现的激素，apelin 在关节软骨代谢中的确切作用尚不清楚。本研究旨在评估 apelin 在关节软骨中的作用。在体外，我们研究了 apelin 对正常软骨细胞增殖和金属蛋白酶（MMPs）和白细胞介素-1β（IL-1β）基因表达的影响。在体内，通过关节内注射 apelin，我们检测了 MMP-3、-9、胶原 II 和 IL-1β在基因和蛋白水平上的表达。此外，我们测量了关节软骨中 ADAMTS-4 和 -5（具有血小板反应蛋白基序的解整合素和金属蛋白酶 4 和 5）和蛋白聚糖的信使 RNA（mRNA）表达。Apelin 刺激软骨细胞增殖，并显著增加 MMP-1、-3、-9 和 IL-1β的 mRNA 水平。体内关节内注射 apelin 上调 MMP-3、-9 和 IL-1β 的表达，并降低胶原 II 的水平。此外，在用 apelin 治疗后，关节软骨中 ADAMTS-4 和 -5 的 mRNA 水平明显增加，并且通过组织学评估发现蛋白聚糖耗竭。这些发现表明，apelin 在软骨代谢中发挥分解代谢作用，是骨关节炎病理生理学的一个危险因素。
