W. Wei, S. Clockaerts, Y. M. Bastiaansen-Jenniskens, L. M. Gierman, S

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Presentation transcript:

Statins and fibrates do not affect development of spontaneous cartilage damage in STR/Ort mice W. Wei, S. Clockaerts, Y.M. Bastiaansen-Jenniskens, L.M. Gierman, S.M. Botter, S.M.A. Bierma-Zeinstra, H. Weinans, J.A.N. Verhaar, M. Kloppenburg, A.-M. Zuurmond, G.J.V.M. van Osch Osteoarthritis and Cartilage Volume 22, Issue 2, Pages 293-301 (February 2014) DOI: 10.1016/j.joca.2013.11.009 Copyright © 2013 Osteoarthritis Research Society International Terms and Conditions

Fig. 1 Effect of treatment on BW and serum metabolic markers. T = 0 weeks represent start of experimental treatment at the age of 8 weeks. Control group received reference diet for 16 weeks. Treatment groups received simvastatin and/or fenofibrate mixed into their diet for 16 weeks. Indicated dosages are intended drug intake/kg BW/day. Combination group received simvastatin 40 mg and fenofibrate 80 mg. (A) Body weight, (B) Serum triglyceride, (C) Serum total cholesterol. Values indicate mean + SD (n = 11–12 mice per group). Horizontal dashed line: mean value of T = 0. * = P < 0.01 vs Control group. ** = P < 0.001 vs Control group. Osteoarthritis and Cartilage 2014 22, 293-301DOI: (10.1016/j.joca.2013.11.009) Copyright © 2013 Osteoarthritis Research Society International Terms and Conditions

Fig. 2 Effect of simvastatin and/or fenofibrate on serum inflammatory markers. Control group received reference diet. Treatment groups received simvastatin and/or fenofibrate mixed with their diet for 16 weeks. Indicated dosages are intended drug intake/kg BW/day. Combination group received simvastatin 40 mg and fenofibrate 80 mg. (A) Serum IL-1α, (B) Serum MIP1α, (C) Serum IL-10 and (D) SAA levels. T = 0: values before treatment at the age of 8 weeks. Horizontal dashed line indicates the mean value at the start of treatment (T = 0). Values indicate mean + SD (n = 11–12 mice per group). Osteoarthritis and Cartilage 2014 22, 293-301DOI: (10.1016/j.joca.2013.11.009) Copyright © 2013 Osteoarthritis Research Society International Terms and Conditions

Fig. 3 Histological analysis of effect of simvastatin and/or fenofibrate treatment on cartilage damage in STR/Ort mice. The coronal sections of cartilage in the weight-bearing area of the tibiofemoral compartment of the left knee were stained with thionine and severity of cartilage damage was scored on a scale of 0–6 using the OARSI histological scoring scale. Control group received reference diet for 16 weeks. Treatment groups received simvastatin and/or fenofibrate mixed with their diet for 16 weeks. Indicated dosages are intended drug intake/kg BW/day. Combination group received simvastatin 40 mg and fenofibrate 80 mg. (A) Representative picture of score 0: normal cartilage (B) Representative picture of score 6: Vertical clefs/erosion to the calcified cartilage extending to >75% of the surface. Pictures are taken at 40× magnification. (C) Quantification of OARSI scores of the medial femur. (D) Quantification of OARSI scores of the medial tibia. (E) Number of cell layers in the synovial membrane. Each dot represents an individual mouse (n = 11–12 mice per group) Horizontal line indicates median value per group in C and D. Mean ± SD is shown in E. Osteoarthritis and Cartilage 2014 22, 293-301DOI: (10.1016/j.joca.2013.11.009) Copyright © 2013 Osteoarthritis Research Society International Terms and Conditions

Fig. 4 Effect of simvastatin and/or fenofibrate treatment on subchondral bone plate BV and thickness of the tibia plateau in STR/Ort mice. Control group received reference diet for 16 weeks. Treatment groups received simvastatin and/or fenofibrate mixed with their diet for 16 weeks. Indicated dosages are intended drug intake/kg BW/day. Combination group received simvastatin 40 mg and fenofibrate 80 mg. (A) Subchondral bone plate BV (B) Subchondral bone plate thickness, Values indicate mean + SD (n = 11–12 mice per group). Osteoarthritis and Cartilage 2014 22, 293-301DOI: (10.1016/j.joca.2013.11.009) Copyright © 2013 Osteoarthritis Research Society International Terms and Conditions