期刊
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
卷 88, 期 9, 页码 4206-4213出版社
ENDOCRINE SOC
DOI: 10.1210/jc.2002-021877
关键词
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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-kappaB ligand is essential for osteoclasts and enhances bone resorption, whereas osteoprotegerin (OPG) neutralizes receptor activator of nuclear factor-kappaB 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.
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