Osteoporosis is a major bone disorder that affects both men and women during aging. The pathogenesis is due largely to the increased osteoclast activity which is largely attributed to the increased generation of osteoclasts (osteoclastogenesis). Thus, understanding the cellular and molecular mechanisms in the regulation of osteoclastogenesis is of paramount importance in the battle against osteoporosis. Efforts proposed in this application are directed toward identifying novel targets for the treatment of osteoporosis. Accumulated preliminary data from both in vivo and in vitro studies, indicate a specific and important role of Ca2+/calmodulin dependent kinase II (CaMKII) in the regulation of osteoclastogenesis. Experimental aims are designed to address the hypothesis that CaMKII regulates osteoclastogenesis.
Specific aims to accomplish this are:
Specific Aim 1. Characterization of the roles of different CaMKII subtypes involved in osteoclastogenesis, i. Determine the cellular distribution of different CaMKII subtypes (apha and or gamma) in bone marrow, ii. Characterize CaMKII in cells from CaMKIIalpha mutant mice during osteoclastogenesis, iii. Characterize bone mineral density (BMD) changes in CaMKIIalpha mutant mice. iv. Further characterize the specificity of CaMKII alpha and or gamma in osteoclastogenesis by viral mediated gene transfer.
Specific Aim 2. Determine the molecular mechanisms of CaMKII regulation of osteoclastogenesis, i. Does CaMKII regulate RANKL signaling? ii. Identify the substrates of CamKII in RANKL signaling pathways, iii. Does CaMKII regulate macrophage fusion molecules? Elucidation of the molecular events responsible for CaMKII's involvement in osteoclastogenesis, will reveal detailed molecular mechanisms, which may provide new targets for designing rational therapeutic strategies to combat osteoporosis.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
7K01AG021999-07
Application #
7668895
Study Section
National Institute on Aging Initial Review Group (NIA)
Program Officer
Williams, John
Project Start
2003-09-30
Project End
2010-08-31
Budget Start
2008-08-15
Budget End
2010-08-31
Support Year
7
Fiscal Year
2007
Total Cost
$116,560
Indirect Cost
Name
Palmer College of Chiropractic
Department
Type
Other Domestic Higher Education
DUNS #
075845834
City
Davenport
State
IA
Country
United States
Zip Code
52803
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