Adiponectin associates with markers of cartilage degradation in osteoarthritis and induces production of proinflammatory and catabolic factors through mitogen activated protein kinase pathways
Koskinen, Anna; Juslin, Sami; Nieminen, Riina; Moilanen, Teemu; Vuolteenaho, Katriina; Moilanen, Eeva (2011)
2011
Arthritis Research & Therapy 13 6
R184
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BioMed Central open access
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Introduction
Adiponectin is an adipokine that regulates energy metabolism and insulin sensitivity, but recent studies have pointed also to a role in inflammation and arthritis. The purpose of the present study was to investigate the association and effects of adiponectin on inflammation and cartilage destruction in osteoarthritis (OA).
Methods
Cartilage and blood samples were collected from 35 male OA patients undergoing total knee replacement surgery. Preoperative radiographs were evaluated by Ahlback classification criteria for knee OA. Circulating concentrations of adiponectin and biomarkers of OA, i.e. cartilage oligomeric matrix protein (COMP) and matrix metalloproteinase 3 (MMP-3), were measured. Cartilage samples obtained at the surgery were cultured ex vivo and the levels of adiponectin, nitric oxide (NO), interleukin-6 (IL-6) and metalloproteinases MMP-1 and MMP-3 were determined in the culture media. In addition, the effects of adiponectin on the production of NO, IL-6, MMP-1 and MMP-3 were studied in cartilage and in primary chondrocyte cultures.
Results
Plasma adiponectin levels and adiponectin released from OA cartilage were higher in patients with radiologically most severe OA (Ahlback grades 4-5) than in patients with less severe disease (grades 1-3). Plasma adiponectin concentrations correlated positively with biomarkers of OA, i.e. COMP (r = 0.55, p = 0.001) and MMP-3 (r = 0.34, p = 0.046). Adiponectin was released by OA cartilage ex vivo and it correlated positively with NO (r = 0.43, p = 0.012), IL-6 (r = 0.42, p = 0.018), and MMP-3 (r = 0.34, p = 0.051) production. Further, adiponectin enhanced production of NO, IL-6, MMP-1 and MMP-3 in OA cartilage and in primary chondrocytes in vitro by a mitogen-activated protein kinase (MAPK) dependent manner.
Conclusions
These findings show that adiponectin is associated with and possibly mediates cartilage destruction in OA.
Adiponectin is an adipokine that regulates energy metabolism and insulin sensitivity, but recent studies have pointed also to a role in inflammation and arthritis. The purpose of the present study was to investigate the association and effects of adiponectin on inflammation and cartilage destruction in osteoarthritis (OA).
Methods
Cartilage and blood samples were collected from 35 male OA patients undergoing total knee replacement surgery. Preoperative radiographs were evaluated by Ahlback classification criteria for knee OA. Circulating concentrations of adiponectin and biomarkers of OA, i.e. cartilage oligomeric matrix protein (COMP) and matrix metalloproteinase 3 (MMP-3), were measured. Cartilage samples obtained at the surgery were cultured ex vivo and the levels of adiponectin, nitric oxide (NO), interleukin-6 (IL-6) and metalloproteinases MMP-1 and MMP-3 were determined in the culture media. In addition, the effects of adiponectin on the production of NO, IL-6, MMP-1 and MMP-3 were studied in cartilage and in primary chondrocyte cultures.
Results
Plasma adiponectin levels and adiponectin released from OA cartilage were higher in patients with radiologically most severe OA (Ahlback grades 4-5) than in patients with less severe disease (grades 1-3). Plasma adiponectin concentrations correlated positively with biomarkers of OA, i.e. COMP (r = 0.55, p = 0.001) and MMP-3 (r = 0.34, p = 0.046). Adiponectin was released by OA cartilage ex vivo and it correlated positively with NO (r = 0.43, p = 0.012), IL-6 (r = 0.42, p = 0.018), and MMP-3 (r = 0.34, p = 0.051) production. Further, adiponectin enhanced production of NO, IL-6, MMP-1 and MMP-3 in OA cartilage and in primary chondrocytes in vitro by a mitogen-activated protein kinase (MAPK) dependent manner.
Conclusions
These findings show that adiponectin is associated with and possibly mediates cartilage destruction in OA.
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