| Autor: |
Viereck V; Department of Obstetrics and Gynecology, Georg-August-University of Goettingen, Goettingen, Germany D-37075. viereck@med.uni-goettingen.de, Gründker C, Blaschke S, Niederkleine B, Siggelkow H, Frosch KH, Raddatz D, Emons G, Hofbauer LC |
| Jazyk: |
angličtina |
| Zdroj: |
The Journal of clinical endocrinology and metabolism [J Clin Endocrinol Metab] 2003 Sep; Vol. 88 (9), pp. 4206-13. |
| DOI: |
10.1210/jc.2002-021877 |
| Abstrakt: |
Raloxifene reduces bone loss and prevents vertebral fractures in postmenopausal women. Its skeletal effects are mediated by estrogen receptors (ER) and their modulation of paracrine osteoblastic factors. Receptor activator of nuclear factor-kappa B ligand is essential for osteoclasts and enhances bone resorption, whereas osteoprotegerin (OPG) neutralizes receptor activator of nuclear factor-kappa B ligand. Here, we assessed the effects of raloxifene on OPG production in human osteoblasts (hOB). Raloxifene enhanced gene expression of ER-alpha and progesterone receptor. Moreover, raloxifene increased OPG mRNA levels and protein secretion by hOB in a dose- and time-dependent fashion by 2- to 4-fold with a maximum effect at 10(-7) M and after 72 h (P < 0.001). Treatment with the ER antagonist ICI 182,780 abrogated the effects of raloxifene on OPG production. Moreover, raloxifene enhanced osteoblastic differentiation markers, type 1 collagen secretion, and alkaline phosphatase activity by 3- and 2-fold, respectively (P < 0.001). In addition, raloxifene inhibited expression of the bone-resorbing cytokine IL-6 by 25-45% (P < 0.001). In conclusion, our data suggest that raloxifene stimulates OPG production and inhibits IL-6 production by hOB. Because OPG production increases with osteoblastic maturation, enhancement of OPG production by raloxifene could be related to its stimulatory effects on osteoblastic differentiation. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
|
