دانلود رایگان مقاله کاهش توده استخوان ران در هر دو موش با چربی خون

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.

5. Conclusions

In conclusion, we demonstrated that hyperlipidemia reduced bone formation and enhanced bone resorption, resulting in lower femoral bone mass in mice. We also found higher plasma S1P levels in hyperlipidemia mice and a positive correlation between plasma CTx and S1P levels, indicating S1P may be involved in hyperlipidemia induced abnormal bone metabolism.