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Dietary phosphate restriction decreases stem cell proliferation and subsequent growth potential in neonatal pigs
Lindsey S Alexander1, Avanika Mahajan, Jack Odle
1Laboratory of Developmental Nutrition, Department of Animal Science, North Carolina State University, Raleigh, NC 27695, USA.
Insights
Dietary phosphate restriction in piglets reduces growth and bone development by impairing the proliferation of mesenchymal stem cells (MSC) and satellite cells. This mineral impacts early cell programming, potentially affecting lifelong growth potential.
Area of Science:
- Developmental Biology
- Nutritional Science
- Stem Cell Biology
Background:
- Mesenchymal stem cells (MSC) and satellite cells are crucial for postnatal muscle and bone growth.
- Phosphate (PO(4)) restriction is known to hinder skeletal and muscle tissue development.
- The specific mechanisms by which phosphate affects early cell programming remain largely unexplored.
Purpose of the Study:
- To investigate the impact of dietary phosphate availability on the early programming and proliferation of tissue-specific stem cells in vivo.
- To determine if phosphate deficiency affects mesenchymal stem cell (MSC) and satellite cell proliferation during early development.
Main Methods:
- Twenty piglets were divided into two groups: one receiving a PO(4)-adequate diet and the other a diet with 25% less PO(4)-available for 15 days.
- Daily records of feed intake and body weight were maintained, with blood samples collected every 5 days.
- Cell proliferation was assessed in vivo using bromodeoxyuridine incorporation in mesenchymal stem cells (MSC) and satellite cells.
Main Results:
- Phosphate deficiency led to significantly reduced growth, feed conversion efficiency, and bone mineral content.
- Plasma concentrations of phosphate and parathyroid hormone were lower in the phosphate-deficient group.
- A significant reduction in the proliferation of both mesenchymal stem cells (MSC) (P < 0.01) and satellite cells (P < 0.05) was observed in vivo.
Conclusions:
- Dietary phosphate is critical for the proliferation of tissue-specific stem cells, including mesenchymal stem cells (MSC) and satellite cells, in vivo.
- Phosphate deficiency negatively impacts not only growth and bone development but also the fundamental processes of stem cell proliferation.
- Nutritional programming by dietary phosphate during early development may have long-term implications for an organism's growth potential.
Abstract:
Although mesenchymal stem cells (MSC) and satellite cells are essential for postnatal muscle and bone development and phosphate (PO(4)) 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 PO(4)-adequate diet or a 25% less PO(4)-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, PO(4) 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 PO(4) (P < 0.01) and parathyroid hormone (P < 0.05). In addition to these classical indicators of PO(4) 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 PO(4)-adequate treatment group. These data indicate that in addition to reductions in muscle and bone growth, dietary PO(4) affects proliferation of tissue-specific stem cells in vivo. Nutritional programming of tissue-specific stem cells by dietary PO(4) may have profound implications for life-long growth potential.
