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Publication : Reduced femoral bone mass in both diet-induced and genetic hyperlipidemia mice.

First Author  Chen X Year  2016
Journal  Bone Volume  93
Pages  104-112 PubMed ID  27669658
Mgi Jnum  J:255144 Mgi Id  MGI:6112823
Doi  10.1016/j.bone.2016.09.016 Citation  Chen X, et al. (2016) Reduced femoral bone mass in both diet-induced and genetic hyperlipidemia mice. Bone 93:104-112
abstractText  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 8weeks were placed on either control diet or high-fat diet (HFD) for 12weeks. 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 PPARgamma expression. In conclusion, our study found decreased bone mass in both diet-induced and genetic hyperlipidemia mice.
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