Dietary Phosphate Restriction Decreases Stem Cell Proliferation and Subsequent Growth Potential in Neonatal Pigs

Although mesenchymal stem cells (MSC) and satellite cells are essential for postnatal muscle and bone development and phosphate (PO4) restriction reduces both muscle and skeletal tissue growth, no research to our knowledge has investigated the possible mechanism by which this mineral may affect early cell programming. Twenty piglets obtained at 1 d of age (1.8 +/- 0.3 kg) received either a PO4-adequate diet or a 25% less PO4-available diet over a 15-d trial. Feed intake and body weight were recorded daily and blood samples collected every 5 d. After 15 d, pigs were given an intraperitoneal injection of bromodeoxyuridine 4 h prior to tissue collection. As expected, PO4 deficiency resulted in reduced growth (P < 0.05), feed conversion efficiency (P < 0.05), and bone mineral content (P < 0.05), as well as lower plasma concentrations of both PO4 (P < 0.01) and parathyroid hormone (P < 0.05). In addition to these classical indicators of PO4 deficiency, there was also reduced proliferation of both MSC (P < 0.01) and satellite cells (P < 0.05) in vivo. The expression of osteocalcin mRNA in bone marrow was also 2-fold greater (P < 0.01) within the PO4-adequate treatment group. These data indicate that in addition to reductions in muscle and bone growth, dietary PO4 affects proliferation of tissue-specific stem cells in vivo. Nutritional programming of tissue-specific stem cells by dietary PO4 may have profound implications for life-long growth potential. J. Nutr. 140: 477-482, 2010.