Suppressive Effects of Genistein Dosage and Resistance Exercise on Bone Loss in Ovariectomized Rats.

Nakajima, Daito; Kim, Changsun; Oh, Tae‐Woong; Yang, Chu-Ya; Naka, Tatsuki; Igawa, Shoji; Ohta, Fukio

doi:10.2114/jpa.20.285

Cited by 47 publications

(34 citation statements)

References 25 publications

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“…In the present study on female rats with normal estrogen levels, both low and high doses of genistein treatment were observed to induce significant increase in BMD, BMC and bone volume, as well as inducing thicker and larger trabecular bone in the mandibular subchondral bone. These results were consistent with the above-mentioned studies on appendicular bone or vertebrae [17,18,20,[30][31][32][33][34][35][36] , indicating that the effect of genistein on mandibular subchondral bone is similar to that on appendicular bone or vertebrae. Similar to the biphasic effects of estrogen depending on dosage [37] , genistein was also observed to have a biphasic cell proliferative response, stimulation at low concentrations and inhibition at high concentrations [38][39][40] .…”

Section: Effect Of Er Silencing On the Effect Of Genistein Treatmentsupporting

confidence: 91%

“…ERα and ERβ siRNA were able to knockdown 72% and 80% of ER expression, respectively. As shown in Figure 6 and [18,20,[30][31][32][33][34][35][36] . Similarly, oral administration of genistein (54 mg·kg -1 ·d -1 ) increased BMD of the spine and hip in osteopenic postmenopausal Caucasian women with an observation period of 24 months [17] .…”

Section: Effect Of Er Silencing On the Effect Of Genistein Treatmentmentioning

confidence: 99%

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Dose-dependent effects of genistein on bone homeostasis in rats' mandibular subchondral bone

Xing

Wang

et al. 2011

Acta Pharmacol Sin

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Aim: To investigate the effect of genistein on bone homeostasis in mandibular subchondral bone of rats. Methods: Female SD rats were administered with genistein (10 and 50 mg/kg) or placebo by oral gavage for 6 weeks. Then the animals were sacrificed, and histomorphology and micro-structure of mandibular condyle were examined using HE staining and micro-CT analysis, respectively. The expression levels of alkaline phosphatase (ALP), osteocalcin (OC), osteoprotegerin (OPG), the receptor activator of nuclear factor κB ligand (RANKL) and estrogen receptors (ERs) in mandibular condyle were detected using real-time PCR. Cultured osteoblasts were prepared from rat mandibular condyle for in in vitro study. The cells were treated with genistein (10 -7 or 10 -4 mol/L) for 48 h. The expression of the bone homeostasis-associated factors and estrogen receptors (ERs) was detected using realtime PCR, and ER silencing was performed. Results: At both the low-and high-doses, genistein significantly increased the bone mineral density (BMD) and bone volume, and resulted in thicker subchondral trabecular bone in vivo. In both in vivo and in vitro study, the low-dose genistein significantly increased the expression of ALP, OC and OPG, but decreased the expression of RANKL and the RANKL/OPG ratio. The high-dose genistein decreased the expression of all these bone homeostasis-associated factors. Both the low and high doses of genistein significantly increased the expression of ERβ, while ERα expression was increased by the low dose genistein and decreased by the high dose genistein. ERβ silencing abrogated most of the effects of genistein treatment. Conclusion: In rat mandibular condylar subchondral bone, low-dose genistein increases bone formation and inhibit bone resorption, while excess genistein inhibits both bone formation and resorption. The effects of genistein were predominantly mediated through ERβ.

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Section: Effect Of Er Silencing On the Effect Of Genistein Treatmentsupporting

confidence: 91%

Section: Effect Of Er Silencing On the Effect Of Genistein Treatmentmentioning

confidence: 99%

Dose-dependent effects of genistein on bone homeostasis in rats' mandibular subchondral bone

Xing

Wang

et al. 2011

Acta Pharmacol Sin

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“…(34) Research on ovariectomized animals have shown that combining isoflavones with exercise training can be beneficial in increasing BMD to a greater extent than either intervention used exclusively. (20,22,35) In addition, several clinical trials have shown that a combination of exercise and HRT results in an increase in BMD that is more than either intervention used exclusively. (36) This study is the first to suggest that the combined intervention of isoflavone and walking exercise for 1 year may partly prevented bone loss in postmenopausal women.…”

Section: Discussionmentioning

confidence: 99%

Effects of Isoflavone and Exercise on BMD and Fat Mass in Postmenopausal Japanese Women: A 1-Year Randomized Placebo-Controlled Trial

Oka

Tabata

et al. 2006

Journal of Bone and Mineral Research

121

116

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The combined intervention of isoflavone intake and walking exercise over 1 year in postmenopausal Japanese women exhibited a trend for a greater effect on prevention of bone loss at the total hip and Ward's triangle regions. Introduction:The additive effects of isoflavones and exercise on bone and lipid metabolism have been shown in estrogen-deficient animals. In this study, we determined the effects of isoflavone intake, walking exercise, and their interaction on bone, fat mass, and lipid metabolism over 1 year in postmenopausal Japanese women. Materials and Methods: A total of 136 postmenopausal women at <5 years after the onset of menopause were randomly assigned to four groups: (1) placebo, (2) walking (45 minutes/day, 3 days/week) with placebo, (3) isoflavone intake (75 mg of isoflavone conjugates/day), and (4) combination of isoflavone plus walking. BMD, fat mass, serum lipid, and serum and urinary isoflavone concentrations were assessed. Results: A significant main effect of isoflavone on the reduction in trunk fat mass was obtained at 12 months. Significant main effects of walking on the reduction in fat mass in the whole body and the trunk were observed at 3, 6, and 12 months and that in the legs and arms at 6 and 12 months. Serum high-density lipoprotein (HDL)-cholesterol concentration significantly increased by 12 months after the walking and the combined intervention. After 12 months, a significant main effect of isoflavone on BMD was observed only at Ward's triangle. Walking prevented bone loss at the total hip and the Ward's triangle to significant degrees. The effect of the combined intervention on BMD at total hip and Ward's triangle regions was greater than that of either alone. No significant interaction was observed between isoflavone and walking in any measurements recorded during the study. Conclusions: Our study suggest that combined intervention of 75 mg/day of isoflavone intake and walking exercise 3 times/week for 1 year showed a trend for a greater effect on BMD at total hip and Ward's triangle regions than either alone. Intervention with isoflavone in postmenopausal Japanese women showed a modest effect on BMD compared with those in Westerners. Further studies over longer treatment duration that include assessment of BMD at various regions are necessary to ascertain the clinical significance of the combined intervention of isoflavone plus walking in postmenopausal women.

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“…Phytoestrogens such as genistein, resveratrol, and quercetin are widely distributed in human and animal diet and have chemopreventive properties against estrogen-responsive diseases, including inhibition of tumor cell growth (Setchell & Cassidy 1999, Miodini et al 1999, Mitchell et al 1999, Xing et al 2001, lowering serum cholesterol, and prevention of bone loss in rodents (Mizutani et al 2000, Nakajima et al 2001, Wattel et al 2003. Genistein is the most potent estrogenic compound in soy and soy products.…”

Section: Introductionmentioning

confidence: 99%

Effects of genistein, resveratrol, and quercetin on steroidogenesis and proliferation of MA-10 mouse Leydig tumor cells

Chen

Nagpal

Stocco

et al. 2007

Journal of Endocrinology

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This study was performed to compare the effects of three well-known phytoestrogens such as genistein, resveratrol, and quercetin on steroidogenesis in MA-10 mouse tumor Leydig cells. Addition of genistein or resveratrol to MA-10 cells resulted in decreases in the cAMP-stimulated progesterone secretion, but quercetin had an opposite response. Steroidogenic acute regulatory (StAR) mRNA expression and StAR promoter activity in transiently transfected MA-10 cells were significantly reduced by genistein or resveratrol, but increased by quercetin. Genistein was found to inhibit MA-10 cell proliferation, while resveratrol and quercetin had no effect. Quercetin-induced increase in cAMP-stimulated progesterone secretion was reversed by ICI 182,780, an estrogen receptor (ER) antagonist. However, ICI 182,780 had no effect on cAMP plus quercetin-stimulated StAR promoter activity. To examine whether non-ER factors are associated with quercetin-stimulated progesterone production, we treated MA-10 cells with EGTA to deprive them of extracellular Ca 2C. We found that EGTA inhibited quercetin-plus cAMP-stimulated progesterone secretion and StAR promoter activity. Blocking of Ca 2C influx through L-or Ttype voltage-gated Ca 2C channels with verapamil or mibefradil respectively, attenuated quercetin-stimulated progesterone secretion, while they had no effect on quercetinplus cAMP-stimulated StAR promoter activity. Blocking of intracellular Ca 2C efflux by sodium orthovanadate, a Ca 2C -pump inhibitor, blocked quercetin-plus cAMP-stimulated progesterone secretion and StAR promoter activity in MA-10 cells. Finally, EGTA or vanadate reduced quercetin and cAMP-increased in StAR mRNA expression in MA-10 cells, while ICI 182,780 had no effect. Taken together, these results indicate that phytoestrogens have differential effects on steroidogenesis in MA-10 cells.

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Suppressive Effects of Genistein Dosage and Resistance Exercise on Bone Loss in Ovariectomized Rats.

Cited by 47 publications

References 25 publications

Dose-dependent effects of genistein on bone homeostasis in rats' mandibular subchondral bone

Dose-dependent effects of genistein on bone homeostasis in rats' mandibular subchondral bone

Effects of Isoflavone and Exercise on BMD and Fat Mass in Postmenopausal Japanese Women: A 1-Year Randomized Placebo-Controlled Trial

Effects of genistein, resveratrol, and quercetin on steroidogenesis and proliferation of MA-10 mouse Leydig tumor cells

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