Effects of 17beta-estradiol, tamoxifen and raloxifene on the protein and mRNA expression of interleukin-6, transforming growth factor-beta1 and insulin-like growth factor-1 in primary human osteoblast cultures.
We investigated the effects of 17betaestradiol and two selective estrogen receptor modulators, tamoxifen and raloxifene, on the expression and release of constitutive and interleukin-1-stimulated interleukin (IL)-6, transforming growth factor-beta1 (TGF-beta1) and insulin-like growth factor-1 by osteoblasts in primary culture from trabecular bone of healthy post-menopausal women. After 24 h incubation with 10(-8) M concentration of these compounds, there was no decrease in: a) the constitutive or IL-1beta-induced levels of IL-6 protein released to culture medium; b) the constitutive IL-6 mRNA expression after incubation of osteoblasts with 10(-8) M 17betaestradiol or 10(-8) M tamoxifen for 1, 3, 6, 24 or 30 h. Although a decrease after 30 h of treatment with 10(-8) M, raloxifene was found in mRNA IL-6 expression, and this fact was not reflected by a decrease in the release of IL-6 protein to the culture medium after 48 h of incubation with 10(-8) M or 10(-7) M raloxifene. Tumoral growth factorTGF-betal expression was not influenced by incubation with these compounds. Gene expression of IGF-I increased following 24 or 30 h incubation with 10(-8) M 17beta-estradiol and 30 h incubation with raloxifene. Tamoxifen did not affect IGF-I expression. In conclusion, the effects of estradiol or tamoxifen on bone metabolism do not appear to be mediated through the regulation of osteoblast IL-6 release or synthesis, but raloxifene produces a decrease in mRNA IL-6 expression. The actions of estradiol, tamoxifen and raloxifene do not appear to be mediated by tumoral growth factor TGF-beta1. On the other hand, an increase in IGF-I synthesis induced by raloxifene and estradiol could mediate, in part, the effects of these compounds on bone.
Méndez-Dávila
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Bone Pathophysiology Laboratory, Fundación Jiménez Diaz, Madrid, Spain.
García-Moreno
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Turbì
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de la Piedra
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D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D018929:Cell Culture Techniques; D004958:Estradiol / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis*; D015850:Interleukin-6 / Q000096:biosynthesis*; D008875:Middle Aged; D010006:Osteoblasts / Q000502:physiology*; D010024:Osteoporosis / Q000503:physiopathology; D017698:Postmenopause; D012333:RNA, Messenger / Q000096:biosynthesis; D020849:Raloxifene Hydrochloride / Q000494:pharmacology*; D013629:Tamoxifen / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*; D053773:Transforming Growth Factor beta1
D018931:Antineoplastic Agents, Hormonal; D004965:Estrogen Antagonists; D015850:Interleukin-6; D012333:RNA, Messenger; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D013629:Tamoxifen; D020849:Raloxifene Hydrochloride; D004958:Estradiol; D007334:Insulin-Like Growth Factor I