Gap junctions formed by connexin 43 (Cx43) play an important role in transmitting signals between bone cells essential for bone formation and remodeling. Osteocytes express large amounts of Cx43 compared with other bone cell types; however, they only form gap junctions with other osteocytes through the tips of their dendritic processes. Our preliminary data suggests that in addition to gap junctions, primary osteocytes and osteocyte-1 like MLO-Y4 cells express functional Cx43-forming hemichannels and these hemichannels mediate the immediate response of osteocytes to mechanical stress. The central hypothesis is that hemichannels formed by Cx43 have essential, yet distinct functions from gap junctions in the regulation of the osteocytic response to mechanical strain, and a5-integrin regulates the opening of hemichannels.
Two specific aims will be pursued: 1) Identify the essential roles that Cx43-forming hemichannels play in osteocyte responses to mechanical stress; 2) Determine if a5 integrin regulates the opening of hemichannels induced by fluid flow shear stress. The innovative and significant aspects of this proposal are the discovery of novel mechanisms for unconventional roles of Cx43-forming hemichannels in regulating osteocyte response to mechanical strain. This study will provide comprehensive training using biochemical, molecular, and functional techniques combined with unique mechanical engineering applications. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
1F31AR053468-01
Application #
7062185
Study Section
Special Emphasis Panel (ZRG1-F10 (29))
Program Officer
Sharrock, William J
Project Start
2006-02-01
Project End
2009-01-31
Budget Start
2006-02-01
Budget End
2007-01-31
Support Year
1
Fiscal Year
2006
Total Cost
$32,057
Indirect Cost
Name
University of Texas Health Science Center San Antonio
Department
Biochemistry
Type
Other Domestic Higher Education
DUNS #
800772162
City
San Antonio
State
TX
Country
United States
Zip Code
78229
Batra, Nidhi; Burra, Sirisha; Siller-Jackson, Arlene J et al. (2012) Mechanical stress-activated integrin ?5?1 induces opening of connexin 43 hemichannels. Proc Natl Acad Sci U S A 109:3359-64
Siller-Jackson, Arlene J; Burra, Sirisha; Gu, Sumin et al. (2008) Adaptation of connexin 43-hemichannel prostaglandin release to mechanical loading. J Biol Chem 283:26374-82