|CHEN, JINRAN - ACNC/UAMS
|LAZARENKO, OXANA - ACNC/UAMS
|BLACKBURN, MICHAEL - ACNC/UAMS
|BADEAUX, JAMIE - ACNC/ACH
|BADGER, THOMAS - ACNC/UAMS
|RONIS, MARTIN - ACNC/UAMS
Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/4/2009
Publication Date: 8/26/2009
Citation: Chen, J., Lazarenko, O.P., Blackburn, M.L., Badeaux, J.V., Badger, T.M., Ronis, M.J. 2009. Infant formula promotes bone growth in neonatal piglets by enhancing osteoblastogenesis through bone morphogenic protein signaling. Journal of Nutrition. 139(10):1839-1847.
Interpretive Summary: Formulas such as milk-based or soy-based are largely consumed by infants world wild. Although American Academy of Pediatrics recommends breast feeding for infants, and where breast feeding is not possible, it recommends milk-based formula, with soy-based formula as the third choice for those intolerant of cow's milk. Soy-based formula constitutes 20-25% of all infant formula in the USA and much more in Asian countries. The safety of infant formulas should be always prioritized. We have recently comprehensively studied the affect of milk-based and soy-based formulas relative to breast feeding on skeletal growth using newborn piglet infant model. We did not find differences in body weight and development of reproductive tissue in response to different formulas. However, we have demonstrated that both formulas promoted bone growth with much greater effect of soy-based formula compared to breast feeding. We found that the effects of formulas on bone are due to their ability to expend osteoblast progenitors in bone marrow. Furthermore, we demonstrated that bone-forming signals are elevated by formulas and are associated with osteoblast differentiation. We therefore concluded that the effects of formulas on bone are positive, and indicated the appearance of such new components in serum with corresponding infant diets. We believe that the data represent an important advance in our mechanistic understanding of consuming infant formulas on bone growth, and imply skeletal programming effects by early life nutrition. We also consider that the study will be accessible to both scientists and clinicians within the biomedical research community, and dietary manipulation in the first year of life may be the earliest phase for intervention of osteoporosis occurring in later life.
Technical Abstract: Relatively few studies have examined the effects of formula feeding relative to breast-feeding on bone in the neonate. Using peripheral quantitative CT scan and histomorphometric analysis, we demonstrated that neonatal piglets fed with soy-based formula (SF) and cow milk-based formula (MF) for 21 or 35 d had greater bone mineral density and content than breast-fed piglets (BF) (P < 0.05). Osteoblast numbers and bone formation rate at postnatal d 35 were greater in SF compared with other groups (P < 0.05), whereas osteoclast numbers were lower in both MF and SF groups than in the BF group (P < 0.05). Osteoblastogenesis was greater in ex vivo bone marrow cell cultures from SF than in MF or BF piglets (P < 0.05). Bone formation markers in serum were greater, whereas bone resorption markers were lower in the MF- and SF-fed groups than in the BF group (P < 0.05). Bone morphogenic protein (BMP) 2 and alkaline phosphatase mRNAs were upregulated in the MF and SF groups compared with the BF group (P < 0.05), whereas receptor activator of NF- B ligand was downregulated (P < 0.05). Extracellular signal-regulated kinase, p38, Smad1/5/8 phosphorylation, and runt-related transcription factor 2 expression were greater in bone from the MF and SF groups compared with the BF group (P < 0.05). In vitro studies showed that 2.5% serum from SF- or MF-fed piglets was able to stimulate osteoblast differentiation but not in the presence of the BMP blocker noggin. Therefore, formula feeding promoted bone growth compared with BF. SF piglets had the highest bone volume over tissue volume. This suggests that SF-fed piglets may have the best quality bone. The anabolic effects of SF on bone appear to be mediated through enhanced BMP signaling.