The Oxysterol, 27-Hydroxycholesterol, Links Cholesterol Metabolism to Bone Homeostasis Through Its Actions on the Estrogen and Liver X Receptors
| Autor: | Michihisa Umetani, Ryan D. Michalek, Jeffrey C. Rathmell, Erik R. Nelson, Diane Gesty-Palmer, Xiaojuan Wang, Matthew K. Howe, Glenda L. Evans, Sundeep Khosla, Donald P. McDonnell, Carolyn D. DuSell |
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| Rok vydání: | 2011 |
| Předmět: |
Receptors
Steroid medicine.medical_specialty Oxysterol Osteoporosis Biology Bone and Bones Bone resorption Bone remodeling Mice chemistry.chemical_compound Endocrinology Internal medicine medicine Animals Homeostasis Bone Resorption Liver X receptor General Endocrinology Liver X Receptors Bone mineral Osteoblasts Cell Differentiation Osteoblast Orphan Nuclear Receptors medicine.disease Hydroxycholesterols Sterols Cholesterol medicine.anatomical_structure Receptors Estrogen chemistry 27-Hydroxycholesterol |
| Zdroj: | Endocrinology. 152:4691-4705 |
| ISSN: | 1945-7170 0013-7227 |
| DOI: | 10.1210/en.2011-1298 |
| Popis: | Osteoporosis and age-related bone loss are important public health concerns. Therefore, there is a high level of interest in the development of medical interventions and lifestyle changes that reduce the incidence of osteoporosis and age-related bone loss. Decreased bone mineral density is associated with high cholesterol, and patients on statins have increased bone mineral densities, strongly implicating cholesterol as a negative regulator of bone homeostasis. In this study, using both molecular and pharmacological approaches, we have been able to demonstrate that the primary cholesterol metabolite, 27-hydroxycholesterol, through its actions on both estrogen receptors and liver X receptors, decreases osteoblast differentiation and enhances osteoclastogenesis, resulting in increased bone resorbtion in mice. Induction of the short heterodimer partner protein by estrogens in osteoblasts can attenuate the liver X receptor-mediated actions of 27-hydroxycholesterol in bone. These data establish a mechanistic link between cholesterol and bone quality, highlight an unexpected target of estrogens in osteoblasts, and define a signaling axis, the therapeutic exploitation of which is likely to yield novel antiosteoporotic drugs. |
| Databáze: | OpenAIRE |
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