Location: Arkansas Children's Nutrition CenterTitle: Soy-based formula promotes bone growth in neonatal piglets by inducing osteo-progenitors to differentiate into osteoblasts via enhanced BMP2 signaling Author
Submitted to: American Society for Bone and Mineral Research
Publication Type: Abstract Only
Publication Acceptance Date: 6/1/2008
Publication Date: 9/15/2008
Publication URL: http://www.asbmr.org/secure/FINAL_Abstract_Book.pdf
Citation: Chen, J., Lazarenko, O.P., Blackburn, M.L., Badger, T.M., Ronis, M.J. 2008. Soy-based formula promotes bone growth in neonatal piglets by inducing osteo-progenitors to differentiate into osteoblasts via enhanced BMP2 signaling [abstract]. American Society for Bone and Mineral Research. 636. Available: http://www.asbmr.org/secure/FINAL_Abstract_Book.pdf. Interpretive Summary:
Technical Abstract: Despite consumption of soy infant formula by 20% of infants in the United States and of soy products by children in most Asian countries, the majority of studies of soy effects on bone in both human and experimental animal models have focused on adults, particularly postmenopausal females. There have been no studies conducted on soy effects on immediate postnatal bone growth and maintenance. Moreover, the molecular mechanisms underlying soy effects have not been well elucidated. In the current study we used neonatal piglets as a model of human infants. Both male and female piglets were breast-fed (BF) or fed dairy-based formula (MF) or soy-based formula (SF) (n = 6/group) from birth until postnatal day 35. After sacrifice, blood, bone, bone marrow, and other target tissues were collected for analysis. Bone quality and growth rate were assessed by peripheral quantitative computerized tomography and dynamic histomorphometry of the left tibia. Results showed that bone mineral density, content, and cortical thickness were all greater (P<0.05) in the SF group compared to the BF group. The MF group had minor effects compared to BF. Osteoblast numbers and bone formation rate were increased (P<0.05) in the SF group when compared to BF group; whereas, osteoclast numbers were decreased. Osteoblastogenesis was increased (P<0.05) in the SF group in ex vivo bone marrow cell cultures. Alkaline phosphatase and osteocalcin, bone formation markers in serum, were increased (P<0.05); whereas, the bone resorption marker CrossLaps was decreased in the SF group compared to BF group. Real-Time PCR results demonstrated that BMP2 was up-regulated, but RANKL was down-regulated in the SF group compared to BF group (P<0.05). Western Blots showed up-regulation of ERK, p38, Smad1/5/8, and RUNX2 from bone samples in both SF and MF groups compared to BF group (P<0.05). Treatment of C2C12 and ST2 cells with 2.5% serum from SF piglets showed increased (P<0.05) osteoblast differentiation compared to serum from BF piglets. These data indicate that SF has significant effects on promotion of bone growth, and these effects are mediated through enhancing of BMP2 signaling leading to increased osteoblast differentiation.