A low dose of daidzein acts as an ERβ‐selective agonist in trabecular osteoblasts of young female piglets

Abstract

The role of estrogens and estrogen-like molecules, including isoflavones, in regulating bone cell activities is essential in understanding the etiology and treatment of post-menopausal osteoporosis. Although estrogen replacement (HRT) has been the main therapy used to prevent and treat osteoporosis, there are concerns about its safety. Isoflavones have attracted attention to their potential roles in osteoporosis prevention and treatment. We have compared the effects of the isoflavone daidzein (1 nM), which has no effect on tyrosine kinases, and 17beta-estradiol (1 nM) on the development and function of cultured osteoblasts isolated from long bones of young female piglets. Daidzein increased ALP activity, osteocalcin secretion, and mineralization, while E2 increased only ALP activity. The content of ERbeta and osteoprotegerin secretion by control cells gradually increased during osteoblast differentiation, whereas the ERalpha and RANK-L content decreased. Daidzein enhanced only the nuclear ERbeta whereas estradiol increased both ERalpha and ERbeta. Daidzein and estradiol increased osteoprotegerin and RANK-L secretion. Daidzein had a more pronounced effect than did estradiol. Daidzein and estradiol increased the membrane content of RANK-L and the nuclear content of runx2/Cbfa1. Daidzein enhanced the nuclear content of progesterone and vitamin D receptors but not as much as did estradiol. All the effects of daidzein were blocked by ICI 182,780. We conclude that a low concentration of daidzein may exert its anti-resorptive action by increasing the activity of porcine mature osteoblasts via ERbeta, by regulating runx2/Cbfa1 production, and by stimulating the secretion of key proteins involved in osteoclastogenesis, such as osteoprotegerin and RANK-ligand.

Effects of soybean isoflavone on intestinal antioxidant capacity and cytokines in young piglets fed oxidized fish oil

“…Our findings support the potential of ISF as an intestinal protective agent in young piglets with its attenuation of intestinal damage induced by oxidative stress. Although several studies have evaluated the effectiveness of ISF on piglets (de Wilde et al, 2004;Mau et al, 2008;Goerke et al, 2012), none of these studies examined the effectiveness of ISF treatment on the oxidative stress and immune function of the piglets.…”

Enhancing Effect of Daidzein on the Differentiation and Mineralization in Mouse Osteoblast-like MC3T3-E1 Cells

“…Studies about the eŠect of daidzein on the bone formation and osteoblast function have been reported. [13][14][15]17) These studies demonstrated that daidzein can stimulate the early diŠerentiation of osteoblasts and act on osteoblasts via estrogen receptor MC3T3 E1 cells are pre-osteoblastic cells that undergo osteoblastic diŠerentiation and mineralization when grown in the presence of b-GP and L-AA. It is known that proliferation, matrix maturation and mineralization are three sequential processes in the diŠerentiation of osteoblasts.…”

“…15) On the action of daidzein on osteoblast function, daidzein is shown to act on some cytokine products such as interleukin-6 (IL-6), osteoprotegerin (OPG) and receptor activator of NF-kB ligand (RANKL) via estrogenreceptor pathway in hFOB 1.19 cell line 16) and trabecular osteoblasts isolated from young female piglets. 17) In our previous study, daidzein is shown to enhance the viability and stimulate the late stage of diŠerentia-tion of osteoblasts isolated from newly born rat calvariae. 18) Moreover, the increased production of bone morphogenetic protein (BMP2) is considered to mediate the eŠect.…”

When nutrition interacts with osteoblast function: molecular mechanisms of polyphenols

“…To understand the molecular mechanisms it is necessary that transcript and protein levels are both assessed at the same time and in the same model. Some isoflavones also have the capacity to increase ALP activity and mineralisation (42,43,69) . It has been shown that incubation with 1 nM-daidzein for 48 h increased the nuclear content of Runx2/Cbfa1 protein in porcine osteoblasts (69) .…”