Estrogen directly attenuates human osteoclastogenesis, but has no effect on resorption by mature osteoclasts
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Estrogen directly attenuates human osteoclastogenesis, but has no effect on resorption by mature osteoclasts. / Sørensen, M G; Henriksen, K; Dziegiel, Morten Hanefeld; Tankó, L B; Karsdal, M A.
In: D N A and Cell Biology, Vol. 25, No. 8, 08.2006, p. 475-83.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - Estrogen directly attenuates human osteoclastogenesis, but has no effect on resorption by mature osteoclasts
AU - Sørensen, M G
AU - Henriksen, K
AU - Dziegiel, Morten Hanefeld
AU - Tankó, L B
AU - Karsdal, M A
PY - 2006/8
Y1 - 2006/8
N2 - Estrogen deficiency arising with the menopause promotes marked acceleration of bone resorption, which can be restored by hormone replacement therapy. The inhibitory effects of estrogen seem to involve indirect cytokine- mediated effects via supporting bone marrow cells, but direct estrogen-receptor mediated effects on the bone-resorbing osteoclasts have also been proposed. Little information is available on whether estrogens modulate human osteoclastogenesis or merely inhibit the functional activity of osteoclasts. To clarify whether estrogens directly modulate osteoclastic activities human CD14+ monocytes were cultured in the presence of M-CSF and RANKL to induce osteoclast differentiation. Addition of 0.1-10 nM 17beta-estradiol to differentiating osteoclasts resulted in a dose-dependent reduction in tartrate resistant acid phosphatase (TRACP) activity reaching 60% at 0.1 nM. In addition, 17beta-estradiol inhibited bone resorption, as measured by the release of the C-terminal crosslinked telopeptide (CTX), by 60% at 0.1 nM, but had no effect on the overall cell viability. In contrast to the results obtained with differentiating osteoclasts, addition of 17beta-estradiol (0.001-10 nM) to mature osteoclasts did not affect bone resorption or TRACP activity. We investigated expression of the estrogen receptors, using immunocytochemistry and Western blotting. We found that ER-alpha is expressed in osteoclast precursors, whereas ER- beta is expressed at all stages, indicating that the inhibitory effect of estrogen on osteoclastogenesis is mediated by ER-alpha for the major part. In conclusion, these results suggest that the in vivo effects of estrogen are mediated by reduction of osteoclastogenesis rather than direct inhibition of the resorptive activity of mature osteoclasts.
AB - Estrogen deficiency arising with the menopause promotes marked acceleration of bone resorption, which can be restored by hormone replacement therapy. The inhibitory effects of estrogen seem to involve indirect cytokine- mediated effects via supporting bone marrow cells, but direct estrogen-receptor mediated effects on the bone-resorbing osteoclasts have also been proposed. Little information is available on whether estrogens modulate human osteoclastogenesis or merely inhibit the functional activity of osteoclasts. To clarify whether estrogens directly modulate osteoclastic activities human CD14+ monocytes were cultured in the presence of M-CSF and RANKL to induce osteoclast differentiation. Addition of 0.1-10 nM 17beta-estradiol to differentiating osteoclasts resulted in a dose-dependent reduction in tartrate resistant acid phosphatase (TRACP) activity reaching 60% at 0.1 nM. In addition, 17beta-estradiol inhibited bone resorption, as measured by the release of the C-terminal crosslinked telopeptide (CTX), by 60% at 0.1 nM, but had no effect on the overall cell viability. In contrast to the results obtained with differentiating osteoclasts, addition of 17beta-estradiol (0.001-10 nM) to mature osteoclasts did not affect bone resorption or TRACP activity. We investigated expression of the estrogen receptors, using immunocytochemistry and Western blotting. We found that ER-alpha is expressed in osteoclast precursors, whereas ER- beta is expressed at all stages, indicating that the inhibitory effect of estrogen on osteoclastogenesis is mediated by ER-alpha for the major part. In conclusion, these results suggest that the in vivo effects of estrogen are mediated by reduction of osteoclastogenesis rather than direct inhibition of the resorptive activity of mature osteoclasts.
KW - Blotting, Western
KW - Bone Resorption
KW - Estradiol
KW - Estrogen Receptor alpha
KW - Estrogen Receptor beta
KW - Humans
KW - Immunohistochemistry
KW - Osteoclasts
U2 - 10.1089/dna.2006.25.475
DO - 10.1089/dna.2006.25.475
M3 - Journal article
C2 - 16907645
VL - 25
SP - 475
EP - 483
JO - DNA and Cell Biology
JF - DNA and Cell Biology
SN - 1044-5498
IS - 8
ER -
ID: 47556704