| Autor: |
McCauley, L. K., Tözüm, T. F., Kozloff, K. M., Koh-Paige, A. J., Chen, C., Demashkieh, M., Cronovich, H., Richard, V., Keller, E. T., Rosol, T. J., Goldstein, S. A. |
| Předmět: |
|
| Zdroj: |
Connective Tissue Research; Jan2003 Supplement 1, Vol. 44, p250-263, 14p |
| Abstrakt: |
Estrogen has protective effects on the skeleton via its inhibition of bone resorption. Mechanisms for these effects and the selectivity to the estrogen receptor α (ERα) or ERβ are unclear. The purpose of our study was to determine the impact of the ERα on skeletal metabolism using murine models with targeted disruption of the ERα and β. Mice generated by homologous recombination and Cre/ lox P technology yielding a deletion of the ERα exon 3 were evaluated and also crossed with mice with a disruption of the exon 3 of the ERβ to result in double ERα and ERβ knockout mice. Skeletal analysis of long bone length and width, radiographs, dual X-ray absorptiometry, bone histomorphometry, micro computerized tomography, biomechanical analysis, serum biochemistry, and osteoblast differentiation were evaluated. Male ERα knockout mice had the most dramatic phenotype consisting of reduced bone mineral density (BMD), and bone mineral content (BMC) of femurs at 10 and 16 weeks and 8-9 months of age. Female ERα knockout mice also had reduced density of long bones but to a lesser degree than male mice. The reduction of trabecular and cortical bone in male ERα knockout mice was statistically significant. Male double ERα and ERβ knockouts had similar reductions in bone density versus the single ERα knockout mice suggesting that the ERα is more protective than the ERβ in bone. In vitro analysis revealed no differences in osteoblast differentiation or mineralized nodule formation among cells from ERα genotypes. These data suggest that estrogens are important in skeletal metabolism in males; the ERα plays an important role in estrogen protective effects; osteoblast differentiation is not altered with loss of the ERα; and compensatory mechanisms are present in the absence of the ERα and/or another receptor for estrogen exists that mediates further effects of estrogen on the skeleton. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
|
