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ARS Home » Southeast Area » Little Rock, Arkansas » Microbiome and Metabolism Research Unit » Research » Publications at this Location » Publication #308668

Title: Soy protein isolate inhibits high fat diet-induced senescence pathways in osteoblasts to maintain bone acquisition in rats

item CHEN, JINRAN - 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 Badger, Thomas
item RONIS, MARTIN - Arkansas Children'S Nutrition Research Center (ACNC)

Submitted to: American Society for Bone and Mineral Research
Publication Type: Abstract Only
Publication Acceptance Date: 5/8/2014
Publication Date: 2/1/2015
Citation: Chen, J., Lazarenko, O.P., Blackburn, M.L., Badger, T.M., Ronis, M.J. 2015. Soy protein isolate inhibits high fat diet-induced senescence pathways in osteoblasts to maintain bone acquisition in rats. Journal of Bone and Mineral Research. 29(S1):Presentation Number:SU0185. Available at

Interpretive Summary:

Technical Abstract: Chronic consumption by experimental animals of a typical Western diet high in saturated fats and cholesterol during postnatal life has been demonstrated to impair skeletal development. However, the underlying mechanism by which high fat, energy dense diets affect bone-forming cell phenotypes is poorly understood. Using peripheral quantitative computerized tomography (pQCT) analysis of the proximal tibial and vertebrae compression testing, we show that male weanling rats fed a diet containing 45% fat and 0.5% cholesterol made with casein (HF-Cas) for 6 weeks displayed lower bone mineral density and strength compared to AIN-93G-fed dietary controls. Substitution of casein with soy protein isolate (SPI) in the high fat diet (HF-SPI) prevented these effects. The bone-sparing effects of SPI were associated with prevention of HF-Cas-induced osteoblast senescence pathways through suppression of p53/p21 signaling pathways. HF-Cas-fed rats had increased caveolin-1 and down-regulated Sirt1 leading to activation of PPAR' and p53/p21; whereas, rats fed HF-SPI suppressed caveolin-1and activated Sirt1 to de-acetylate PPAR' and p53 in bone. Treatment of osteoblastic cells with non-esterified free fatty acid (NEFA) (a mixture of NEFA with individual NEFA ratio and concentration similar to their appearance in HF rat serum) increased cell senescence signaling pathways. An isoflavone mixture (at concentrations identical to that found in SPI diet rat serum) significantly blocked activation of senescence-associated beta-galactosidase (SA-beta-gal) and PPAR'/p53/p21 by NEFA. Over expression of PPAR' in osteoblastic cells triggered p53/SA-beta-gal senescent signaling. Finally, replicative senescent osteoblastic cells and bone marrow mesenchymal ST2 cells exhibited similar behavior to cells treated with NEFA and bone cells in vivo in rats fed HF-Cas diet. These results suggest that: 1) high concentrations of NEFA occurring with HF intake are mediators of osteoblast cell senescence leading to impairment of bone development and acquisition; and 2) the molecular mechanisms underlying the SPI-protective effects involve isoflavone-induced inhibition of osteoblastic cell senescence to prevent HF-induced bone impairments.