Reduced femoral bone mass in both diet-induced and genetic hyperlipidemia mice |
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| Affiliation: | 1. Laboratory of Endocrinology and Metabolism, Department of Endocrinology, West China Hospital, Sichuan University, 610041, People''s Republic of China;2. Department of Endocrinology, West China Hospital, Sichuan University, 610041, People''s Republic of China;1. Cardiovascular Research Institute, University of California, San Francisco, CA 94158, USA;2. Department of Pharmaceutical Chemistry, University of California, San Francisco, CA 94158, USA;3. Department of Philosophy, Ohio University, Athens, OH 45701, USA;4. Membrane Transport Biophysics Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA;5. Swedish Center for Research and Innovation, Swedish Health Services, Seattle, WA 98122, USA;1. Centre for Statistics in Medicine, Botnar Research Centre, University of Oxford, Windmill Road, Oxford OX3 7LD, United Kingdom;2. Department of Anesthesia & Clinical Epidemiology, Michael DeGroote School of Medicine, Faculty of Health Sciences, McMaster University, Perioperative Research Group, Population Health Research Institute, Hamilton, Canada;3. Department of Biostatistics, Michael DeGroote School of Medicine, Faculty of Health Sciences, McMaster University, Perioperative Research Group, Population Health Research Institute, Hamilton, Canada;1. Clinical and Molecular Osteoporosis Research Unit, Department of Orthopedics and Clinical Sciences, Lund University, Skåne University Hospital, SE-205 02 Malmö, Sweden;2. Department of Physiology and Clinical Sciences, Lund University, Skåne University Hospital, SE-205 02 Malmö, Sweden;1. Institute for Physical Activity and Nutrition (IPAN), School of Exercise and Nutrition Sciences, Deakin University, Geelong, Australia;2. Menzies Health Institute Queensland, School of Allied Health Sciences, Griffith University, Gold Coast, Australia;1. Center for Metabolic Bone Disease and Molecular Research, Shriners Hospital for Children, St. Louis, MO 63110, USA;2. Division of Bone and Mineral Diseases, Department of Internal Medicine, Washington University School of Medicine at Barnes-Jewish Hospital, St. Louis, MO 63110, USA |
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| Abstract: | Growing evidence argues for a relationship between lipid and bone metabolisms with inconsistent conclusions. Sphingosine-1-phosphate (S1P) has been recognized as a suitable candidate for possible link between lipid metabolism and bone metabolism. This study was designed to investigate the effects of hyperlipidemia on bone metabolism using diet-induced and genetic-induced hyperlipidemia animal models and to explore whether S1P is involved. Wild-type mice and low-density lipoprotein receptor gene deficient (LDLR−/−) mice at age of 8 weeks were placed on either control diet or high-fat diet (HFD) for 12 weeks. Bone structural parameters were determined using microCT. Cross-linked type I collagen (CTx) and S1P levels in plasma were measured by ELISA methods. Bone marrow cells from wild type and LDLR−/− mice were induced to differentiate into osteoblasts, osteoclasts and adipocytes respectively. Gene expressions in distal femur metaphyses and cultured cells were studied by qRT-PCR. Moderate hypercholesterolemia was found in HFD-feeding mice; severe hypercholesterolemia and moderate hypertriglyceridemia were present in LDLR−/− mice. Femoral trabecular bone mass was reduced in both diet-induced and genetic hyperlipidemia mice. Mice feeding on HFD showed higher CTx levels, and mice with hyperlipidemia had elevated S1P levels. Correlation analysis found a positive correlation between CTx and S1P levels. Lower Runx2 expression and higher TRAP expression were found in both diet-induced and genetic hyperlipidemia mice, indicating decreased osteoblastic functions and increased osteoclastic functions in these mice. Bone marrow cells from LDLR−/− mice also showed increased adipogenesis and inhibited osteogenesis accompanied by enhanced PPARγ expression. In conclusion, our study found decreased bone mass in both diet-induced and genetic hyperlipidemia mice. |
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