Effects of 17β-estradiol, tamoxifen and raloxifene on the protein and mRNA expression of interleukin-6, transforming growth factor-β1 and insulin-like growth factor-1 in primary human osteoblast cultures

Abstract

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.

Effect of vibration on osteoblastic and osteoclastic activities: Analysis of bone metabolism using goldfish scale as a model for bone

“…In addition, the receptor mRNA expression of estrogen that is related to osteoblastic growth and differentiation (Okazaki et al, 2002;Wiren et al, 2002;Mendez-Davila et al, 2004) was examined as an osteoblastic marker because we recently detected an estrogen receptor (ER) in the scale and determined that it had a co-relationship with osteoblastic activity (Yoshikubo et al, 2005). The mRNA expression of TRAP, which is an osteoclastic marker, was also examined and compared with the enzyme activity of TRAP.…”

Endogenous estrogen may prevent bone loss in postmenopausal hemodialysis patients throughout life

“…Estrogen is well known to directly inhibit bone resorption [3]. In addition, estrogen activates osteoblasts both directly and indirectly via the action of growth factors such as IGF-I and -II [5]. Thus, estrogen is thought to decrease bone resorption and increase bone formation in postmenopausal hemodialysis patients.…”

“…Estrogen deficiency stimulates the proliferation and differentiation of osteoclast precursors, and activates mature osteoclasts [3,4]. In addition, estrogen activates osteoblasts both directly and indirectly via growth factors such as insulin-like growth factor (IGF) I and II [5]. For these reasons, estrogen deficiency after menopause leads to a decrease of BMD.…”

Responses of Urinary N-Telopeptide and Renal Calcium Handling to PTH Infusion after Treatment with Estrogen, Raloxifene, and Tamoxifen

“…The beneficial effects of tamoxifen and raloxifene on bone mass are of somewhat lower magnitude compared to those induced by a standard dose of estrogen [23][24][25], consistent with their intermediate effects on bone turnover [22][23][24]26], while some studies have addressed the action of the EAAs on cytokines in postmenopausal women [27,28] and on human osteoclasts and osteoblasts in vitro [29,30]. However, the effects of raloxifene and tamoxifen on PTHmediated bone resorption and levels of circulating resorbing cytokines and how they compare with estrogen are unknown.…”