CHIANG MAI UNIVERSITY JOURNAL OF NATURAL SCIENCES

Volume 19, No. 04, Month OCTOBER, Year 2020, Pages 811 - 832

Effect of leptin alone and in combination with il1? on human chondrocytes in a pellet culture system

Thanyaluck Phitak, Sasimol Udomruk, Kanchanit Boonmaleerat, Peraphan Pothacharoen, Dumnoensun Pruksakorn, Prachya Kongtawelert

Abstract Download PDF

Osteoarthritis is the most common cause of disability among elderly, with obesity being a risk factor. The mechanical force on load-bearing joints in obese patients is known to induced Osteoarthritis development, however, low load-bearing joints in obese patients have also been found to develop Osteoarthritis. Leptin is a systemic hormone, associated with body-weight, and therefore may be the link between obesity and Osteoarthritis. This study aimed to investigate the effect of leptin on primary chondrocyte metabolism in a pellet culture system. The pellets were treated with IL1β or leptin (0.1-10µg/ml) or IL1β and leptin (0.1-10µg/ml) for 21 days. During that period, sulfated glycosaminoglycans (sGAGs) and hydroxyproline released in culture media and remaining in the pellets, as well as the expressions of ACAN, COL2A1, COL1A1, MMP3, MMP13 genes and MMP3, MMP13 enzymes were measured. Additionally, sGAGs and collagen accumulation in the extracellular matrix was determined by histological analysis. Leptin (1.0-10µg/ml) was able to reduce the ECM molecule contents, both sGAGs and collagen, through up-regulation of MMPs expression, down-regulation of ACAN expression and induction of the dedifferentiation stage of chondrocytes. The effect of 10µg/ml leptin was similar to IL1β, the main cytokine involved in cartilage degradation. Interestingly, leptin had an additive effect with IL1β on the reduction of pellet ECM molecule contents. This study shows that leptin can induce cartilage breakdown by down regulation of ECM molecules and up regulation of protease enzymes and has an additive effect with IL1β on cartilage degradation.

Keywords

Osteoarthritis, Chondrocyte, IL1?, Leptin, Pellet culture

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