Bone formation, either through de novo formation or fracture repair, appears to involve the immediate and rapid generation of brown adipose from progenitors within peripheral nerves. However, the purpose of these cells, and whether they contribute to the process of bone formation, is still unknown. In this application we propose that brown adipose tissue plays a critical role in bone formation through regulating the oxygen tension in the microenvironment, to ultimately expand, recruit, and engraft chondro-osseous progenitors, as well as ensure that the new bone is adequately vascularized and innervated. Thus this transient brown adipose tissue, through both its unique ability to rapidly and efficientl burn oxygen, as well as its capacity to secrete many growth factors, suggests that it may be a cell that is critical to this process. We will test this hypothesis by using an animal model that depletes both white and brown adipocytes of the starting material necessary for electron transport, thus preventing this process. Further, we will determine if blocking the activation of the hypoxia induced pathway, in brown adipose tissue will suppress bone formation, and finally we will directly measure whether brown adipose tissue secretes soluble factors essential for expansion and migration of osteoprogenitors. With completion of this work, we will have demonstrated a direct link between blood triglyceride-lipid levels and the ability to induce heterotopic ossification or bone repair.

Public Health Relevance

We hypothesize that tBAT functionally contributes to bone formation through regulation of oxygen pathways essential for expansion and recruitment of progenitors. Further we propose that tBAT enables this functionality by forming oxygen gradients through uncoupled aerobic respiration and by activation of hypoxia inducible factor (HIF) regulated pathways.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AR063779-01A1
Application #
8573688
Study Section
Skeletal Biology Structure and Regeneration Study Section (SBSR)
Program Officer
Sharrock, William J
Project Start
2013-07-01
Project End
2015-06-30
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
1
Fiscal Year
2013
Total Cost
$166,281
Indirect Cost
$60,031
Name
Baylor College of Medicine
Department
Pediatrics
Type
Schools of Medicine
DUNS #
051113330
City
Houston
State
TX
Country
United States
Zip Code
77030