Bone Development Lab


Bone Development Lab

The Bone Development Laboratory studies how early life dietary factors influence skeletal development to optimize peak bone mass and bone function.  The group leverages a wide array of animal and cell models, molecular, and physiology techniques, and human subjects to address questions relevant to bone health and to early life onset diseases such as degenerative bone disorders and obesity. Working in a multidisciplinary, collaborative environment, the team applies tools such as peripheral quantitative CT-scan, micro-CT scan, bone histomorphometric analysis, and animal models to gather a broader picture of physiological or pathophysiological function of bone.  Clinical studies include evaluation of bone development from controlled feeding studies, and how bone is impacted by maternal and child obesity.

By understanding the fundamental biology and regulatory systems that define bone endocrinology and health, the Lab aims to provide the evidence base needed to craft effective strategies to thwart disease and improve health and development of children and adults.

 

Group Members

Jin-Ran Chen, M.D., Ph.D.
Haijun Zhao, Ph.D.
Oxana P. Lazarenko, M.D.

 

Recent Studies

Blueberry/Phenolic Acids, Maternal Obesity, and Bone Health

Dietary factors such as blueberry (BB)-derived phenolic acids and soy protein isolate have been shown to influence skeletal health by affecting bone formation and resorption processes. While the preponderance of evidence for BB-associated outcomes derive from animal models, mounting evidence supports effects of dietary factors on the bone in human studies. The Lab has discovered that hippuric acid (HA) and 3-(3-hydroxyphenyl) propionic acid (3-3-PPA), two phenolic acid (PA) metabolites derived from BB pigment polyphenols that appear in the serum of BB diet-fed rats, are bioactive and dose-dependently promote bone growth in mice and in bone cell cultures (human and rodent). Our preliminary studies implicate G-protein coupled receptor 109A (GPR109A) in mediating bone cell senescence and formation/resorption effects of HA and 3-3-PPA. Our current studies are testing the hypothesis that bone-active blueberry phenolic acids regulate osteoblast and osteoclast activities via the GPR109A. Our ongoing clinical studies of BB feeding in pre-adolescent children will test the idea that short-term BB exposure increases blood and urine markers of bone formation, while reducing markers of resorption.

Both experimental and clinical studies indicate that maternal obesity is associated with poor skeletal development and bone health in offspring. Our lab has demonstrated that maternal high fat diet consumption prior to and during pregnancy in mice and rats is associated with impaired embryonic/neonatal skeletal development. Using bone cell-type specific gene knock mouse models, the tem is currently testing hypothesis that maternal obesity impairs fetal bone development via increased Ezh2 and subsequent decreased SATB2 expression (thus, reduced SATB2-mediated osteoblastic cell differentiation).