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

Acta Pharmacol Sin. 2011 Dec;32(12):1498-504. doi: 10.1038/aps.2011.135. Epub 2011 Oct 31.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Absorptiometry, Photon
  • Animals
  • Base Sequence
  • Bone Density
  • Bone Development*
  • Cholesterol, Dietary / administration & dosage*
  • DNA Primers
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Gene Expression Profiling
  • Mice
  • Oligonucleotide Array Sequence Analysis
  • Osteoporosis / etiology*
  • Ovariectomy
  • Rats
  • Rats, Sprague-Dawley
  • Real-Time Polymerase Chain Reaction


  • Cholesterol, Dietary
  • DNA Primers