Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.
Adipokines Leptin and Adiponectin Correlate with Matrix Metalloproteinases and Interleukin-6 in Synovial Fluid From Osteoarthritis Patients and Enhance Their Production in Osteoarthritic Cartilage Ex Vivo.
Vuolteenaho1, Katriina, Koskinen1, Anna, Juslin1, Sami, Nieminen1, Riina, Moilanen2, Teemu, Moilanen1, Eeva
Adipokines leptin and adiponectin were first discovered to be produced by adipose tissue and to regulate energy metabolism and apetite. Interestingly, they have recently been found also in inflamed joints and related to the regulation of inflammatory responses. In arthritis, proteolytic degradation of cartilage is mediated by matrix metalloproteinases (MMPs) and interleukin-6 (IL-6) contributes to joint inflammation. In the present study, we investigated the effects of leptin and adiponectin on human OA cartilage, and further, assessed the association of leptin and adiponectin to MMPs and IL-6 in synovial fluid from osteoarthritis patients.
Cartilage samples for tissue culture were collected from OA patients undergoing total knee replacement surgery. The effects of leptin and adiponectin on MMP and IL-6 production in cartilage were studied in tissue culture experiments and in primary OA chondrocytes and the signaling pathways involved were studied by pharmacological means. Synovial fluid samples were obtained from 100 OA patients (62 females, BMI 30.8±0.6kg/m2, age 70.0±1.0 years; mean±SEM), and concentrations of leptin, adiponectin, MMPs and IL-6 were measured by immunoassay.
Leptin and adiponectin enhanced production of MMPs and IL-6 in OA cartilage and in primary OA chondrocytes in vitro. Leptin-induced MMP-1, -3 and -13 and IL-6 productions were dependent on activation of MAP kinase JNK. In addition, p38 was involved in the leptin-induced MMP-1 and MMP-13 production and ERK1/2 pathway in MMP-1 production. Adiponectin enhanced IL-6, MMP-1 and MMP-3 production in OA cartilage culture was mediated by p38. In addition, Erk1/2 and JNK mediated adiponectin-induced production of IL-6 while contribution of these pathways to MMP-1 and MMP-3 production was smaller and did not reach statistical significance.
To evaluate if the stimulatory effect of these adipokines on IL-6 and MMPs in OA cartilage ex vivo could be translated in vivo, the concentrations of leptin, adiponectin, MMPs and IL-6 were determined in synovial fluid from OA patients. Synovial fluid leptin correlated positively with MMP-1 (r=0.41, p<0.001) and MMP-3 (r=0.51, p<0.001) as well as with IL-6 (r=0.33, p=0.002). There was also an association between adiponectin and IL-6 (r=0.39, p<0.001), MMP-1 (r=0.31, p=0.004) and MMP-3 (r=0.27, p=0.011).
The findings support the idea of leptin and adiponectin as catabolic and proinflammatory factors in the pathogenesis of OA, and as possible link between obesity and osteoarthritis.
To cite this abstract, please use the following information:
Vuolteenaho, Katriina, Koskinen, Anna, Juslin, Sami, Nieminen, Riina, Moilanen, Teemu, Moilanen, Eeva; Adipokines Leptin and Adiponectin Correlate with Matrix Metalloproteinases and Interleukin-6 in Synovial Fluid From Osteoarthritis Patients and Enhance Their Production in Osteoarthritic Cartilage Ex Vivo. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :1786