Adiponectin is a potential catabolic mediator in osteoarthritis cartilage

Department of Internal Medicine, Seoul National University Bundang Hospital, 166 Gumi-ro, Bundang-gu, Seongnam-si, Gyeonggi-do, Korea, 463-707.
Arthritis research & therapy (Impact Factor: 3.75). 12/2010; 12(6):R231. DOI: 10.1186/ar3218
Source: PubMed


Adiponectin has been implicated in the pathogenesis of osteoarthritis (OA). We studied the effects of adiponectin on the OA cartilage homeostasis.
Immunohistochemical analysis was performed to evaluate differential expression of adiponectin receptors (AdipoRs) in nonlesional and lesional areas of OA cartilage. Cartilage and chondrocytes from the knee joints of primary OA patients were cultured in the presence of adiponectin (0~30 μg/ml). The levels of total nitric oxide (NO), matrix metalloproteinase (MMP)-1, -3, and -13, and tissue inhibitor of metalloproteinase (TIMP)-1 were measured in the conditioned media. The levels of inducible NO synthase (iNOS) and MMPs were determined with the quantitative real-time reverse transcription-polymerase chain reaction. The concentrations of collagenase-cleaved type II collagen neoepitope (C1-2C) were determined in the supernatant of adiponectin-stimulated OA cartilage explants. The effects of kinase and NOS inhibitors were evaluated in the adiponectin-stimulated chondrocytes.
The expression levels of both AdipoR1 and AdipoR2 were significantly higher in lesional than in nonlesional areas of OA cartilage. The increased rate of AdipoR1-positive chondrocytes was twice that of AdipoR2-positive chondrocytes when compared between nonlesional and lesional areas. Adiponectin-stimulated OA chondrocytes showed increased total NO and MMP-1, -3, and -13 levels compared with nonstimulated cells. The TIMP-1 level was not affected. The C1-2C levels were increased by adiponectin in OA cartilage explant culture. AMP-activated protein kinase (AMPK) and c-Jun N-terminal kinase (JNK) inhibitors (compound C and SP600125) significantly suppressed adiponectin-induced production of total NO and MMP-1, -3, and -13. Inducible NOS inhibitors enhanced the expression of the adiponectin-induced MMPs.
Adiponectin causes matrix degradation in OA cartilage and increases MMPs and iNOS expression via the AMPK and JNK pathways in human OA chondrocytes. The catabolic effects of adiponectin may be counteracted by NO.

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    • "While alterations of adiponectin level were noted in OA cartilage and synovial fluid (Honsawek and Chayanupatkul, 2010; Koskinen et al., 2011; Yusuf et al., 2011), the role of this adipokine in OA development remains controversial. A study by Kang and colleagues suggests that that adiponectin promotes chondrocyte catabolism by upregulating MMPs and NOS2 levels via AMPK and JNK pathways (Kang et al., 2010). Others have suggested a chondroprotective function for adiponectin, demonstrating its role in upregulating inhibition of metalloproteinase 2 (TIMP2) and downregulating MMP13 (Chen et al., 2006; Yusuf et al., 2011). "
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