Effect of candidate mediators regulated by exercise on osteoarthritis (OA) in the mouse model

G. Schulze-Tanzil, Department of Special Orthopaedic and Trauma Surgery, Laboratory for Experimental Orthopaedic Surgery, Charité, CBF, Berlin.

Abstract: Muscular activity can lead to a melioration of osteoarthritis. However, which mediators are modulated by exercise, ageing and gender in osteoarthritis patients remains unclear. Therefore, the interplay between particular exercise-regulated candidate mediators, complement activation and cartilage will be analysed to assess their influence on osteoarthritis progression using a mouse model and in vitro/situ analysis of human samples. Exercise-dependent mediators will be investigated in a surgically induced early osteoarthritis mice model (medial collateral ligament and meniscus transection). A whole body vibration based training protocol will be developed and applied to adult female and male mice (> 2,5 month old) for 6-12 weeks post surgical osteoarthritisinduction. The control group receives no training. Subsequently, the expression (as well as zone- and lesion-dependent distribution) of mediators/receptors which might be chondroprotective and associated with physical activity such as IL-6, IL-101,2, complement factors, and the mechano-growth factor IGF-IEc will be studied in the OAK mice joint cartilage, other joint tissues, blood and Musculus quadriceps femoris samples in response to the training conditions. Particularly, the activation and regulation of complement activity, which has been strongly implicated in osteoarthritis3,4,5will be analysed in view of the training procedures and using complement inhibitors. Concerning complement activity/regulation split fragments (C3a, C5a), anaphylatoxin receptors (C3aR, C5aR) and complement inhibiting regulatory proteins (CRPs) will be analysed. For comparison of results, deduced from the animal study, human cartilage samples (derived from OA cartilage versus healthy cartilage) will be used (age 40-80 years, female and male patients) to analyse the expression profile of the same mediators in human cartilage and age- and gender-related differences. Stimulation of cultured human chondrocytes with recombinant mediators will be used to estimate the effect of particular muscle-derived mediators on chondrocytes and samples from the clinical trial (SP6).

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