TY - JOUR
T1 - DT56a stimulates gender-specific human cultured bone cells in vitro
AU - Somjen, Dalia
AU - Katzburg, Sara
AU - Lieberherr, M.
AU - Hendel, David
AU - Yoles, Israel
N1 - Funding Information:
This work was supported by a grant from the faculty of science, Ma-hidol University. S.C. and T.D. were supported by scholarships from the Center of Excellence on Environmental Health and Toxicology, Science & Technology Postgraduate Education and Research Development Office (PERDO), Ministry of Education. T.B. and T.T. were supported by scholarships from the Faculty of Science, Mahidol University.
Funding Information:
This work, including the efforts of Choowong Auesukaree, was funded by Faculty of Science, Mahidol University.
Funding Information:
ACKNOWLEDGMENTS We thank Maleeya Kruatrachue, Metha Meetam (Mahidol University), and Saranya Phunpruch (King Mongkut?s Institute of Technology Ladkrabang) for helpful suggestions, Nisarut Udom for help with the preliminary experiments, and Ferdinand Carlo Warg for editing the manuscript. This work was supported by a grant from the faculty of science, Mahidol University. S.C. and T.D. were supported by scholarships from the Center of Excellence on Environmental Health and Toxicology, Science& Technology Postgraduate Education and Research Development Office (PERDO), Ministry of Education. T.B. and T.T. were supported by scholarships from the Faculty of Science, Mahidol University. FUNDING INFORMATION This work, including the efforts of Choowong Auesukaree, was funded by Faculty of Science, Mahidol University.
PY - 2006/1/1
Y1 - 2006/1/1
N2 - DT56a found to have SERM-like properties is used for the treatment of menopausal symptoms and osteoporosis. In vivo experiments demonstrated that DT56a displayed selective estrogenic activity; it stimulated creatine kinase (CK) specific activity in the skeletal tissues but not on the uterus of ovariectomized rats. DT56a, when applied together with estradiol-17β (E2), completely inhibited the E2-stimulated CK, as demonstrated by other SERMs. DT56a stimulated bone formation in a rat model as measured by histological and histomorphometrical parameters. In a clinical study, administration of DT56a (Femarelle) resulted in a considerable elevation of bone mineral density and relief of menopausal symptoms. The aim of the present study was to analyze the effects of DT56a in vitro on human-derived bone cultured osteoblasts (Ob), by measuring its effects, at different concentrations, on DNA synthesis, CK and alkaline phosphatase (ALP) specific activities as well as changes in intracellular [Ca2+]i concentrations. DT56a stimulated CK and DNA synthesis in both pre- and post-menopausal female Ob with maximal effect at 100 ng/ml for both age groups. In addition, DT56a stimulated ALP in Ob from both pre- and post-menopausal women with maximal effect at lower dose of 50 ng/ml, with higher response of pre-menopausal cells. Raloxifene (Ral) inhibited all DT56a-stimulated changes in Ob from both age groups. DT56a, when given together with E2, completely antagonized E2-stimulated effects demonstrating its nature as a phyto-SERM. DT56a also, dose dependency, stimulated the intracellular levels of [Ca2+]i with maximal effect at 10 ng/ml. Male-derived Ob did not respond to DT56a in any parameter. In summary, DT56a stimulated sex-specifically female-derived Ob, indicating its unique nature compared to the compounds currently used for postmenopausal osteoporosis by being bone-forming and not only an anti-resorptive agent.
AB - DT56a found to have SERM-like properties is used for the treatment of menopausal symptoms and osteoporosis. In vivo experiments demonstrated that DT56a displayed selective estrogenic activity; it stimulated creatine kinase (CK) specific activity in the skeletal tissues but not on the uterus of ovariectomized rats. DT56a, when applied together with estradiol-17β (E2), completely inhibited the E2-stimulated CK, as demonstrated by other SERMs. DT56a stimulated bone formation in a rat model as measured by histological and histomorphometrical parameters. In a clinical study, administration of DT56a (Femarelle) resulted in a considerable elevation of bone mineral density and relief of menopausal symptoms. The aim of the present study was to analyze the effects of DT56a in vitro on human-derived bone cultured osteoblasts (Ob), by measuring its effects, at different concentrations, on DNA synthesis, CK and alkaline phosphatase (ALP) specific activities as well as changes in intracellular [Ca2+]i concentrations. DT56a stimulated CK and DNA synthesis in both pre- and post-menopausal female Ob with maximal effect at 100 ng/ml for both age groups. In addition, DT56a stimulated ALP in Ob from both pre- and post-menopausal women with maximal effect at lower dose of 50 ng/ml, with higher response of pre-menopausal cells. Raloxifene (Ral) inhibited all DT56a-stimulated changes in Ob from both age groups. DT56a, when given together with E2, completely antagonized E2-stimulated effects demonstrating its nature as a phyto-SERM. DT56a also, dose dependency, stimulated the intracellular levels of [Ca2+]i with maximal effect at 10 ng/ml. Male-derived Ob did not respond to DT56a in any parameter. In summary, DT56a stimulated sex-specifically female-derived Ob, indicating its unique nature compared to the compounds currently used for postmenopausal osteoporosis by being bone-forming and not only an anti-resorptive agent.
KW - Creatine kinase
KW - DT56a
KW - Estradiol
KW - Human bone cells
KW - Raloxifene
UR - http://www.scopus.com/inward/record.url?scp=30944457312&partnerID=8YFLogxK
U2 - 10.1016/j.jsbmb.2005.08.002
DO - 10.1016/j.jsbmb.2005.08.002
M3 - Article
C2 - 16243521
AN - SCOPUS:30944457312
SN - 0960-0760
VL - 98
SP - 90
EP - 96
JO - Journal of Steroid Biochemistry and Molecular Biology
JF - Journal of Steroid Biochemistry and Molecular Biology
IS - 1
ER -