Tamoxifen attenuates glucocorticoid actions on bone formation in vitro.
Tamoxifen is a synthetic estrogen analog which may regulate osteogenesis in vivo by virtue of its antiglucocorticoid properties. We have examined tamoxifen regulation of glucocorticoid-induced osteogenesis in two different in vitro bone systems: the chicken periosteal osteogenesis model (CPO) and rat bone marrow stromal cells (RBMC). Hormone uptake studies were conducted with the osteosarcoma cell line, ROS 17/2.8. In the CPO model, alkaline phosphatase (AP) activity and collagen synthesis were stimulated by the glucocorticoid dexamethasone (Dex; 0.1 microM). These Dex-mediated effects were inhibited by increasing concentrations of tamoxifen (10-100 microM). Similarly, in the RBMC model, Dex-dependent (0.01 microM Dex) mineralized tissue formation and AP activity were blocked by tamoxifen (0.1 microM). Although tamoxifen inhibited Dex-mediated increases of AP activity in ROS 17/2.8 cells, it did not inhibit uptake of 3H-Dex or of 3H-estrogen. Northern analyses showed that tamoxifen did not affect messenger RNAs (mRNAs) for AP. Tamoxifen did seem to reduce mRNA for collagen type I, but not bone sialoprotein, osteopontin, and osteocalcin. Dex-induced increases for all proteins mRNAs in the RBMC model were not reduced by tamoxifen. Similarly, tamoxifen had no effects on cellular proliferation. We conclude that tamoxifen has no direct effect on gene expression of bone-related proteins of osteoblastic cells. Further, in the ROS 17/2.8 cell line, the antiglucocorticoid properties of tamoxifen do not appear to be mediated through either Dex or estrogen receptors.
Sukhu
B
B
The Samuel Lunenfeld Research Institute of Mount Sinai Hospital, University of Toronto, Ontario, Canada.
Rotenberg
B
B
Binkert
C
C
Kohno
H
H
Zohar
R
R
McCulloch
C A
CA
Tenenbaum
H C
HC
D000469:Alkaline Phosphatase / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001853:Bone Marrow / Q000378:metabolism / Q000502:physiology; D001854:Bone Marrow Cells; D001842:Bone and Bones / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D002478:Cells, Cultured; D002645:Chickens; D003094:Collagen / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004965:Estrogen Antagonists / Q000494:pharmacology*; D005269:Femur / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D015675:Osteocalcin / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects* / Q000502:physiology; D053495:Osteopontin; D010521:Periosteum / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012795:Sialoglycoproteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology*
D004965:Estrogen Antagonists; D005938:Glucocorticoids; D012333:RNA, Messenger; D012795:Sialoglycoproteins; C506897:Spp1 protein, rat; D013629:Tamoxifen; D015675:Osteocalcin; D053495:Osteopontin; D003907:Dexamethasone; D003094:Collagen; D000469:Alkaline Phosphatase