Inhibition of Osteoporosis in Autoimmune Disease Prone MRL/Mpj-Faslpr Mice by N-3 Fatty Acids

Inhibition of Osteoporosis in Autoimmune Disease Prone MRL/Mpj-Fas^lpr Mice by N-3 Fatty Acids

Arunabh Bhattacharya, PhD, Md, Mizanur Rahman, PhD, Jameela Banu, PhD, Richard A. Lawrence, PhD, Howard S. McGuff, DDS, I.R. Garrett, PhD, Michael Fischbach, MD and Gabriel Fernandes, PhD, CNS

Department of Medicine, Division of Clinical Immunology (A.B., M.M.R., J.L.B., R.A.L., M.F., G.F.), San Antonio, Texas
Department of Pathology (H.S.M.), San Antonio, Texas
University of Texas Health Science Center, OsteoScreen, Inc. (I.R.G.), San Antonio, Texas

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Fig. 1. Effect of corn oil and fish oil on antioxidant enzyme activities in spleen tissues of MRL/lpr mice. Values are mean ± SEM for 5 mice/group. Enzyme units are superoxide dismutase—µmol cytochrome C reduced/min, catalase—µmol formaldehyde produced/min, glutathione peroxidase—µmol NADPH oxidized/min, glutathione S-transferase—µmol 1-chloro-2,4-dinitrobenzene-glutathione conjugate formed/min % 100. *significantly different at p < 0.05 by Student’s t test. **significantly different at p < 0.01 by Student’s t test. SOD = superoxide dismutase, CAT = catalase, GPx = glutathione peroxidase, GST = glutathione S-transferase.

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Fig. 2. Effect of corn oil and fish oil on knee joint histology. A. Fish oil diet fed mouse with normal knee joint, B. Fish oil diet fed mouse with minimal inflammatory joint changes, C. Corn oil diet fed mouse with vasculitis in soft tissue adjacent to the joint, D. Corn oil diet fed mouse with focal lymphocytic synovitis and increased thickness of synovial lining cells.

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Fig. 3. RT-PCR analysis of mRNA expression for receptor activator of NF- ${kappa}$ B ligand (RANKL) and osteoprotegerin (OPG) in lymph nodes of mice fed corn oil or fish oil. A marked decrease in RANKL and significant increase in OPG was observed in fish oil-fed mice compared to corn oil-fed mice. B. Relative expression of RANKL and OPG is shown. The intensity of the bands was determined by densitometry using an Alphaimager 200 (Alpha Innotech Corp) imaging system and normalized to Glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Values are mean ± SEM for bands 1–3 and 4–6. Band intensities in fish oil-fed mice are significantly different from corn oil-fed mice at ** p < 0.01 and *** p < 0.001.