High cholesterol diet increases osteoporosis risk via inhibiting bone formation in rats

Abstract

Aim: To investigate the effects of high cholesterol diet on the development of osteoporosis and the underlying mechanisms in rats. Methods: Female Sprague-Dawley rats were randomly separated into 3 groups: (1) the high cholesterol fed rats were fed a high cholesterol diet containing 77% normal diet food, 3% cholesterol and 20% lard for 3 months; (2) ovariectomised (OVX) rats were bilaterally ovariectomised and fed a standard diet; and (3) the control rats were fed the standard diet. Bone mineral density (BMD) of the rats was measured using dual-energy X-ray absorptiometry. Serum levels of oestradiol (E2), osteocalcin (BGP) and carboxy-terminal collagen crosslinks (CTX) were measured using ELISA. Gene expression profile was determined with microarray. Mouse osteoblast cells (MC3T3-E1) were used for in vitro study. Proliferation, differentiation and oxidative stress of the osteoblasts were investigated using MTT, qRT-PCR and biochemical methods. Results: In high cholesterol fed rats, the femur BMD and serum BGP level were significantly reduced, while the CTX level was significantly increased. DNA microarray analysis showed that 2290 genes were down-regulated and 992 genes were up-regulated in this group of rats. Of these genes, 1626 were also down-regulated and 1466 were up-regulated in OVX rats. In total, 370 genes were up-regulated in both groups, and 976 genes were down-regulated. Some of the down-regulated genes were found to code for proteins involved in the transforming growth factor beta (TGF-β)/bone morphogenic protein (BMP) and Wnt signaling pathways. The up-regulated genes were found to code for IL-6 and Ager with bone-resorption functions. Treatment of MC3T3-E1 cells with cholesterol (12.5-50 μg/mL) inhibited the cell proliferation and differentiation in vitro in a concentration-dependent manner. The treatment also concentration-dependently reduced the expression of BMP2 and Cbfa1, and increased the oxidative injury in MC3T3-E1 cells. Conclusion:The results suggest a close correlation between hypercholesterolaemia and osteoporosis. High cholesterol diet increases the risk of osteoporosis, possible via inhibiting the differentiation and proliferation of osteoblasts.

Role of phytoestrogenic oils in alleviating osteoporosis associated with ovariectomy in rats

“…A recent study indicated lipid metabolic disorders with hyperlipidemia and hypercholesterolemia as a distinct risk for osteoporosis in OVX rats (Hassan and AbdelWahhab 2012). A close relation between hyper-cholesterolaemia and osteoporosis was reported, where, high cholesterol diet increases the risk of osteoporosis, through inhibiting the differentiation and proliferation of osteoblasts (You et al 2011).…”

Metabolomic Profiles Delineate Signature Metabolic Shifts during Estrogen Deficiency-Induced Bone Loss in Rat by GC-TOF/MS

“…Cholesterol and its metabolites would suppress the functional activity of osteoblasts and thereby induce reduced bone mineralization to decrease bone formation [41]. By the same token, high cholesterol diet increases the risk of osteoporosis, possible via inhibiting the differentiation and proliferation of osteoblasts in rats, as You et al observed [42]. At present, the drug treatment against osteoporosis can prevent bone loss, as well as lowering cholesterol levels.…”

Preliminary evaluation of serum total cholesterol concentrations in dogs with osteosarcoma

“…In addition, a study on laboratory rats fed high cholesterol diets reported an increased risk for osteoporosis (You et al . ). Osteocalcin, a protein that is produced by mature osteoblasts, has an endocrine role and can affect lipid metabolism through modulation of the adipose tissue and insulin secretion.…”

“…Numerous studies have been performed evaluating the role of both serum and cellular cholesterol concentrations on bone health via a variety of methodologies (cell culture cell lines, animal models as well as clinical samples) in human medicine (Mandal 2015 ). The findings of these studies revealed that: (1) elevated cholesterol concentrations may increase bone turnover (You et al . 2011 );(2) treating osteoblastic cell cultures with varying concentrations of cholesterol inhibits their proliferation and differentiation (You et al .…”