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Title: Dietary factors during early life program bone formation in female rats

Author
item CHEN, JIN-RAN - Arkansas Children'S Nutrition Research Center (ACNC)
item LAZARENKO, OXANA - Arkansas Children'S Nutrition Research Center (ACNC)
item BLACKBURN, MICHAEL - Arkansas Children'S Nutrition Research Center (ACNC)
item SHANKAR, KARTIK - Arkansas Children'S Nutrition Research Center (ACNC)

Submitted to: Federation of American Societies for Experimental Biology Conference
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/15/2016
Publication Date: 5/1/2017
Citation: Chen, J., Lazarenko, O.P., Blackburn, M.L., Shankar, K. 2017. Dietary factors during early life program bone formation in female rats. Federation of American Societies for Experimental Biology Conference. 31(1):376-387. doi:10.1096/fj.201600703R.

Interpretive Summary: Effect of early postnatal life nutrition on adult bone metabolism is not well understood. Here, we fed soy protein isolate (SPI) diet to postnatal day 24 (PND24) weanling female rats for 30 days, and on PND 55, we switched SPI diet to control casein diet until 6 months of age. We investigated rat bone metabolism at 6-month of age. We showed significantly increased bone mass in rats when they were fed SPI diet during early life. We demonstrated that persistent effects of SPI diets on bone metabolism in adult rats may be due to SPI on anti-bone forming cell aging program. These results suggest that short term SPI diet early in life has modest but persistent programming effects on bone formation to prevent bone loss in adult female rats.

Technical Abstract: Nutritional status during intrauterine and early postnatal life impacts the risk of chronic diseases; however, evidence for an association between early life dietary factors and bone health in adults is limited. Soy protein isolate (SPI) may be one such dietary factor that promotes bone accretion during early life with persistent effects into adulthood. In the present study, we fed postnatal day 24 (PND24) weanling female rats a SPI diet for 30 days (ST-SPI), and on PND 55, we switched SPI diet to control casein diet until 6 months of age. Rats then underwent either ovariectomy (OVX) or sham operation, and thereafter either continued to be fed a SPI diet or control diet for 1 or 3 weeks. We showed significantly increased bone mass in 30-day SPI-fed young rats compared to controls. OVX-induced bone loss was associated with increased osteoblastic cell senescence. Both long-term SPI (LT-SPI) (continuous SPI diet throughout life) and short-term SPI diet only in early life (ST-SPI) protected against one week post-OVX-associated bone loss. On the other hand, LT-SPI diet diminished the loss of total, trabecular and cortical BMD, while ST-SPI diet only reduced cortical BMD loss three weeks post-OVX. Persistent and protective effects of SPI diets on OVX-induced bone loss was associated with down-regulation of caveolin-1/p53 mediated senescence pathway in bone. We recapitulated these results in cell cultures. Reprogramming of cellular senescence signaling by SPI-associated isoflavones in osteoblastic cells may explain the persistent effects of SPI on bone. These results suggest that OVX-induced bone loss is due in part to increased osteoblastic cell senescence, and ST-SPI diet early in life has modest but persistent programming effects on bone formation to prevent OVX-induced bone loss in adult female rats.