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Isopropanolic extract of black cohosh stimulates osteoprotegerin production by human osteoblasts.
- Source :
-
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research [J Bone Miner Res] 2005 Nov; Vol. 20 (11), pp. 2036-43. Date of Electronic Publication: 2005 Jul 18. - Publication Year :
- 2005
-
Abstract
- Unlabelled: An isopropanolic extract (iCR) from the rhizomes of Cimicifuga racemosa (black cohosh) is used an alternative in the treatment of menopausal symptoms, and animal studies suggest positive skeletal effects. iCR stimulated osteoblastic OPG protein secretion by 3- to 5-fold as early as 12 h without affecting RANKL expression. The iCR effect, abrogated by the pure estrogen receptor antagonist ICI 182,780, also enhanced ALP activity (4-fold) and osteocalcin expression (3-fold), possibly contributing to the skeletal effects of black cohosh.<br />Introduction: Despite its positive effects on the skeleton, estrogen replacement therapy is no longer recommended as first-line therapy for the prevention and treatment of postmenopausal osteoporosis because it increases cardiovascular, thromboembolic, and breast cancer risk. Recently, herbal therapeutics such as an isopropanolic extract (iCR) from the rhizomes of Cimicifuga (=Actaea) racemosa (black cohosh) are gaining interest as an alternative in the treatment of menopausal symptoms. Whereas animal studies in rats suggest positive skeletal effects, the mechanism of its actions on bone cells remain unclear. RANKL is essential for osteoclast formation and activation, while osteoprotegerin (OPG) neutralizes RANKL.<br />Materials and Methods: In this study, we assessed the effects of iCR on OPG and RANKL mRNA steady-state levels by semiquantitative RT-PCR and on protein production by an ELISA system in human osteoblasts (hOBs).<br />Results: Under serum-free conditions, treatment with iCR increased OPG mRNA levels and protein secretion of hOBs by 2- to 3-fold in a dose-dependent manner, with a maximum effect at a 10(6)-fold dilution of iCR (p < 0.001) after 24-48 h. Time-course experiments indicated a stimulatory effect of iCR on osteoblastic OPG protein secretion by 3- to 5-fold (p < 0.001) as early as 12 h, whereas RANKL expression was very low and was not found to be modulated by iCR. Of note, the stimulatory effect of iCR on OPG production was abrogated by the pure estrogen receptor antagonist ICI 182,780. Moreover, iCR enhanced two osteoblastic differentiation markers, bone-specific alkaline phosphatase activity and osteocalcin expression, by up to 4- and 3-fold, respectively (p < 0.001).<br />Conclusions: Our data suggest that iCR enhances differentiation and increases the OPG-to-RANKL ratio of normal human osteoblasts. These effects may contribute to the positive skeletal effects of black cohosh.
- Subjects :
- 2-Propanol chemistry
Adult
Alkaline Phosphatase metabolism
Carrier Proteins genetics
Cell Differentiation drug effects
Cells, Cultured
Dexamethasone pharmacology
Dose-Response Relationship, Drug
Enzyme Activation drug effects
Estradiol analogs & derivatives
Estradiol pharmacology
Estrogen Antagonists pharmacology
Estrogen Receptor alpha genetics
Estrogen Receptor beta genetics
Female
Fulvestrant
Gene Expression drug effects
Gene Expression genetics
Glycoproteins genetics
Humans
Male
Membrane Glycoproteins genetics
Menopause
Osteoblasts cytology
Osteoblasts metabolism
Osteocalcin genetics
Osteocalcin metabolism
Osteoporosis, Postmenopausal drug therapy
Osteoprotegerin
Plant Extracts therapeutic use
RANK Ligand
RNA, Messenger genetics
RNA, Messenger metabolism
Receptor Activator of Nuclear Factor-kappa B
Receptors, Cytoplasmic and Nuclear genetics
Receptors, Progesterone genetics
Receptors, Tumor Necrosis Factor genetics
Cimicifuga chemistry
Glycoproteins metabolism
Osteoblasts drug effects
Plant Extracts pharmacology
Receptors, Cytoplasmic and Nuclear metabolism
Receptors, Tumor Necrosis Factor metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0884-0431
- Volume :
- 20
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
- Publication Type :
- Academic Journal
- Accession number :
- 16234977
- Full Text :
- https://doi.org/10.1359/JBMR.050716