on December 11, 2003
Published online before print December 11, 2003, doi: 10.1161/01.ATV.0000112023.62695.7f
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on October 20, 2003
Accepted on November 26, 2003
Hyperlipidemia Promotes Osteoclastic Potential of Bone Marrow Cells Ex Vivo
Yin Tintut *;
From Departments of Medicine (Y.T., L.L.D.) and Physiology (S.M., L.L.D.), The David Geffen School of Medicine at UCLA, Los Angeles, CA.
* To whom correspondence should be addressed. E-mail: ytintut{at}mednet.ucla.edu.
Objectives--Osteoporosis is associated epidemiologically with atherosclerosis and hyperlipidemia. We previously found that atherogenic lipids regulate bone formation. To determine whether hyperlipidemia also affects bone resorption, we compared osteoclastogenesis in marrow preosteoclasts derived from hyperlipidemic versus control mice.
Methods--Nonadherent marrow cells from low-density lipoprotein receptor-/- (LDLR-/-)and C57BL/6J mice were cultured with M-CSF and ligand for receptor activator of nuclear factor-kappaB (RANKL). Functional osteoclastic activity, measured as number of resorption pits, was significantly greater in 12-month-old LDLR-/-. Similar results were obtained in 5- and 10-month-old LDLR-/- versus C57BL/6J mice on a high-fat diet. Osteoclastic differentiation, indicated by tartrate resistant acid phosphatase (TRAP) activity, was significantly greater in the 12-month-old LDLR-/-, and there was a trend toward increased TRAP activity in LDLR-/- on a high-fat diet, at ages 5 and 10 months. Osteoclastic parameters correlated with total serum lipoproteins with a possible threshold effect. Osteoporotic human cortical bone stained positive for lipids in the perivascular space of Haversian canals by oil red O. The presence of lipid hydroperoxides was detected in bone marrow from hyperlipidemic mice.
Conclusions--Hyperlipidemia may contribute to osteoporosis via increased osteoclastic bone resorption.
Key words: calcification • osteoclast • atherosclerosis • hyperlipidemia • osteoporosis
This article has been cited by other articles:
 |
|
 |
|
  M. K Schwartz, J. C Lieske, L. W. Hunter, and V. M Miller Systemic injection of planktonic forms of mammalian-derived nanoparticles alters arterial response to injury in rabbits Am J Physiol Heart Circ Physiol, May 1, 2009; 296(5): H1434 - H1441. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. L. Demer and Y. Tintut Vascular Calcification: Pathobiology of a Multifaceted Disease Circulation, June 3, 2008; 117(22): 2938 - 2948. [Full Text] [PDF]
|
|
|
|
 |
|
 M. S. Huang, S. Morony, J. Lu, Z. Zhang, O. Bezouglaia, W. Tseng, S. Tetradis, L. L. Demer, and Y. Tintut Atherogenic Phospholipids Attenuate Osteogenic Signaling by BMP-2 and Parathyroid Hormone in Osteoblasts J. Biol. Chem., July 20, 2007; 282(29): 21237 - 21243. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-H. Hsu, S. A Venners, H. A Terwedow, Y. Feng, T. Niu, Z. Li, N. Laird, J. D Brain, S. R Cummings, M. L Bouxsein, et al. Relation of body composition, fat mass, and serum lipids to osteoporotic fractures and bone mineral density in Chinese men and women Am. J. Clinical Nutrition, January 1, 2006; 83(1): 146 - 154. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. J. Jeffcoate Abnormalities of Vasomotor Regulation in the Pathogenesis of the Acute Charcot Foot of Diabetes Mellitus International Journal of Lower Extremity Wounds, September 1, 2005; 4(3): 133 - 137. [Abstract] [PDF]
|
|
|
|
 |
|
 M. Leslie Many Roads to Ruin Sci. Aging Knowl. Environ., April 28, 2004; 2004(17): ns2 - ns2. [Abstract] [Full Text] [PDF]
|
|