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Estrogens maintain bone mass by regulating expression of genes controlling function and life span in mature osteoclasts
- Source :
- Annals of the New York Academy of Sciences. 1173
- Publication Year :
- 2009
-
Abstract
- Estrogens play a key role in regulation of bone mass and strength by controlling activity of bone-forming osteoblasts and bone-resorbing osteoclasts. Cellular effects of estrogens are mediated predominantly by the action of estrogen receptor alpha (ERalpha). In earlier studies, ablation of the ERalpha gene in mice did not result in osteoporotic phenotypes due to systemic endocrine disturbance and compensatory effects of elevated levels of testosterone. Despite the relatively well-established effects in osteoblasts, little is known about the direct action of estrogen in osteoclasts. Development in the last decade of more sophisticated genetic manipulation approaches opened new possibilities to explore cell-specific roles of nuclear receptors in bone tissue. Recently, we have generated osteoclast-specific ERalpha gene knockout mice and shown that in vivo estrogens directly regulate the life span of mature osteoclasts by inducing the expression of pro-apoptotic Fas ligand (FasL). Inhibitory effects of estrogens on osteoclast function were further studied in vitro. We observed sufficiently detectable ERalpha expression in osteoclasts differentiating from primary bone marrow cells or RAW264 cells, although levels of ERalpha were decreasing during progression of the differentiation into mature osteoclasts. Treatment with estrogens led to reduction in expression of osteoclast-specific genes controlling bone resorption activity. However, estrogens did not affect the size of multinucleated osteoclasts or number of nuclei in a mature osteoclast. In conclusion, in osteoclasts, estrogens function to inhibit bone resorption activity and vitality rather than differentiation.
- Subjects :
- musculoskeletal diseases
medicine.medical_specialty
medicine.drug_class
Ovariectomy
Longevity
Estrogen receptor
Osteoclasts
Biology
General Biochemistry, Genetics and Molecular Biology
Bone resorption
Bone and Bones
Fractures, Bone
Mice
Multinucleate
History and Philosophy of Science
Osteoclast
Bone Density
Internal medicine
medicine
Animals
Estrogen Receptor beta
Humans
Gonadal Steroid Hormones
Life Style
Aged
Regulation of gene expression
Mice, Knockout
General Neuroscience
Estrogen Receptor alpha
Estrogens
Hematopoiesis
Postmenopause
medicine.anatomical_structure
Endocrinology
Primary bone
Gene Expression Regulation
Estrogen
Female
Estrogen receptor alpha
hormones, hormone substitutes, and hormone antagonists
Locomotion
Subjects
Details
- ISSN :
- 17496632
- Volume :
- 1173
- Database :
- OpenAIRE
- Journal :
- Annals of the New York Academy of Sciences
- Accession number :
- edsair.doi.dedup.....f34273820310ffa6325e4dfc81158c0c