Dietary isoflavones act on bone marrow osteoprogenitor cells and stimulate ovary development before influencing bone mass in pre‐pubertal piglets

Abstract

Food containing soybeans provide isoflavone phytoestrogens that can preserve bone mass in postmenopausal women, and prevent bone loss in ovariectomized rats. But their effects on bone remain unclear, particularly on bone formation during growth. Two groups of eight pre-pubertal piglets were fed a basal or an isoflavone-enriched (S800) diet for 6 weeks. The S800 diet contained 800 mg SoyLifetrade mark/kg, providing 2.8 mg isoflavones/kg body weight/day. Several bones were collected and tested for bone strength and density. Bone marrow was collected from humeri together with blood samples and genital tracts. The plasma concentrations of isoflavones were increased in the pigs fed S800, but growth rate, body weight, plasma bone markers, bone mineral density, and strength were all unaffected. In contrast, cultured stromal cells from S800 pigs had more alkaline phosphatase-rich cells and mineralized nodules, secreted more osteocalcin, osteoprotegerin and RANK-L, synthesized more osteoprotegerin, and RANK-L. Cultured mononucleated nonadherent bone marrow cells from S800 pigs developed fewer tartrate-resistant acid phosphatase mononucleated cells (osteoclast progenitors) when cultured with 1,25(OH)(2)D(3), and resorbed a smaller area of dentine slices. Freshly isolated bone marrow osteoclast progenitors from S800 pigs had more caspase-3 cleavage activity, and synthesized less RANK. Both osteoclast and osteoblast progenitors had ERalpha and ERbeta, whose syntheses were stimulated by the S800 diet. The S800 piglets had heavier ovaries with more follicles, but their uterus weight was unaffected. We conclude that dietary isoflavones have no detectable effect on the bone mass of growing female piglets, but act on bone marrow osteoprogenitors via ERs--mainly ERbeta, and stimulate ovary development.

Effects of Resveratrol Supplementation on Bone Growth in Young Rats and Microarchitecture and Remodeling in Ageing Rats

“…While in vitro studies have shown that resveratrol can dose-dependently increase proliferation and differentiation of osteoblastic MC3T3-E1 cells [ 17 ] and can promote human mesenchymal stem cell commitment to the osteogenic lineage through the master osteogenic transcription factor RUNX2 [ 24 , 37 ], our current study demonstrated that resveratrol supplementation for 5 weeks during the rapid growth period in male rats had no significant effects on growth plate thickness, primary spongiosa heights and trabecular bone volume by the end of treatment, suggesting a lack of effect of resveratrol supplementation on the bone mass outcome in growing rats. These findings are in agreement with a previous study using an isoflavone-enriched diet containing soybean extract, daidzein, genistein, and equol in 6-week-old growing female pigs, which also found no significant changes in the growth plate, mineralization or osteoblast/osteoclast densities in long bones [ 38 ]. Furthermore, another study showed no differences in cortical bone measurements in growing rats given different doses of resveratrol (1, 4, 10, 40, and 100 μg/day) [ 39 ].…”

Phytoöstrogene und Knochenstoffwechsel

“…Im Rattenmodellkonnte zumBeispiel gezeigt werden, dass Genisteinebensowie 17-beta-Östradiold urchS timulation des ER-alpha eine Steigerung derK nochendichte bewirkt (9). Im Gegensatzdazu wird deraktivierende Effekt vonIsoflavonenauf die Osteoprogenitorzelleni mK nochenmark vorallemüberden ER-betavermittelt (6). Phytoöstrogene sind darüberh inaus in derL age, denK nochenstoffwechsel auch durchM odulation desV itamin-D-Metabolismus zu beeinflussen.…”