Skeletal Development Laboratory
The Laboratory of Bone Growth and Development broadly examines the direct effects and long term consequences of early nutrition on bone growth, bone quality, fracture risk, attainment of peak bone mass and risk of osteoporosis in the elderly. Major focuses of the laboratory are in understanding the long term consequences of infant formula (cow’s milk formula and soy formula) feeding relative to breast feeding on aspects of bone growth and development; examining the skeletal effects of feeding soy, fruits and vegetables in early development and understanding the effects of maternal and pediatric obesity and high fat diets on bone quality and fracture risk.
|Jin-Ran Chen, PhD
Kartik Shankar, PhD
Aline Andres, PhD
Thomas Badger, PhD
Martin Ronis, PhD
|Oxana Lazarenko, MD
Michael Blackburn, BS
Jian Zhang, PhD
Kelly Mercer, PhD
Formula vs. Breast Feeding
Although breast feeding remains the gold standard, the majority of infants in the U.S.A. are formula-fed. There appear to be significant differences in skeletal development between breast-fed and formula-fed infants. We are interested in determining if these diet-related differences in infants persist into adulthood and affect attainment of peak bone mass. In addition we are interested in identifying novel bone anabolic factors in soy and dairy products using bioactivity directed fractionation with Dr. Wu (Analytical Core). We are examining these questions using pig and rodent models including transgenic and knock out mouse stains analyzed by cutting edge bone-specific techniques in collaboration with the Center for Orthopedic Research at UAMS including CT scanning, dynamic histomorphometry, immunohistochemistry and in situ hybridization in decalcified bone sections and utilizing molecular approaches such as targeted arrays, microarrays and massively parallel sequencing. In addition, pathways involved in anaboilic bone responses are being analyzed in ex-vivo mesenchymal stem cell cultures and in bone cell lines manipulated by stable transfection and siRNA knockdown approaches. Clinical translational studies using CT scanning and DXA are conducted with Drs. Badger and Andres (Clinical Studies Core) in infants from the “Beginnings” and “Glowings” studies.
Early Diet and Attainment of Peak Bone Mass
It is becoming increasingly apparent that early interventions such as exercise and diet may affect attainment of peak bone mass and risk of degenerative bone disease in adults/the elderly. We are interested in examining the long term effects of early fruit and vegetable consumption on risk of osteoporosis. Current work is focused on persistent effects soy and blueberry consumption prior to and during puberty on mesenchymal stem cell proliferation and differentiation in animal models of peak bone mass and post-menopausal bone loss.
Maternal and Pediatric Obesity and Fracture Risk in Infants and Children
The dogma has long been that increased load bearing results in greater bone mineral density (BMD) and stronger bone with increasing body weight. However, more recent studies focused on bone quality have suggested that if weight is removed as a variable, BMD is inversely correlated with % fat mass. There is evidence that high fat diet-driven obesity reduces bone mass and quality in early development associated with increased fracture risk in obese children. In addition, recent studies in animal models suggest that maternal obesity may delay or impair fetal and neonatal bone development. We are studying these questions in rodent models utilizing total enteral nutrition to completely control diet composition and dissociate weight gain from adiposity and clinically in the “Glowings” study. We are focused on the potential roles of adipokines and fatty acids to impair bone formation via inhibition of Wnt signaling and to stimulate bone resorption through induction of RANKL pathways.
NIH Funded Projects
In addition to nutrition-related projects, the laboratory is funded through an NIH, NIAAA R01 grant to Dr. Ronis to determine the potential role of NADPH-oxidase enzymes as the source of reactive oxygen species in bone driving increased bone resorption after chronic alcohol abuse.