Reduced femoral bone mass in both diet-induced and genetic hyperlipidemia mice.
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 PPARγ expression. In conclusion, our study found decreased bone mass in both diet-induced and genetic hyperlipidemia mice.
Laboratory of Endocrinology and Metabolism, Department of Endocrinology, West China Hospital, Sichuan University, 610041, People's Republic of China.
Xiang
X
Chen
Laboratory of Endocrinology and Metabolism, Department of Endocrinology, West China Hospital, Sichuan University, 610041, People's Republic of China.
Chunyu
C
Wang
Laboratory of Endocrinology and Metabolism, Department of Endocrinology, West China Hospital, Sichuan University, 610041, People's Republic of China.
Kun
K
Zhang
Laboratory of Endocrinology and Metabolism, Department of Endocrinology, West China Hospital, Sichuan University, 610041, People's Republic of China.
Ying
Y
Xie
Laboratory of Endocrinology and Metabolism, Department of Endocrinology, West China Hospital, Sichuan University, 610041, People's Republic of China.
Xiao
X
Ji
Department of Endocrinology, West China Hospital, Sichuan University, 610041, People's Republic of China.
Hui
H
Huang
Laboratory of Endocrinology and Metabolism, Department of Endocrinology, West China Hospital, Sichuan University, 610041, People's Republic of China.
Xijie
X
Yu
D050156:Adipogenesis; D000273:Adipose Tissue / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D059305:Diet, High-Fat / Q000009:adverse effects*; D005269:Femur / Q000378:metabolism / Q000473:pathology*; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D006949:Hyperlipidemias / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D009929:Organ Size; D010006:Osteoblasts / Q000378:metabolism / Q000473:pathology; D010010:Osteoclasts / Q000378:metabolism / Q000473:pathology; D010012:Osteogenesis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011973:Receptors, LDL / Q000172:deficiency / Q000378:metabolism
D012333:RNA, Messenger; D011973:Receptors, LDL
Bone metabolism; Hyperlipidemia; Peroxisome proliferator-activated receptor-γ; Sphingosine-1-phosphate