Gap junctions formed by connexin 43 (Cx43) play an important role in transmitting signals betweenbone cells essential for bone formation and remodeling. Osteocytes express large amounts of Cx43compared with other bone cell types; however, they only form gap junctions with other osteocytesthroughthe tips of their dendritic processes. Our preliminary data suggests that in addition to gap junctions, primaryosteocytes and osteocyte-1ike MLO-Y4 cells express functional Cx43-forming hemichannels and thesehemichannels mediate the immediate response of osteocytes to mechanical stress. The central hypothesisis that hemichannels formed by Cx43 have essential, yet distinct functions from gap junctions in theregulation of the osteocytic response to mechanical strain, and a5-integrin regulates the opening ofhemichannels.
Two specific aims will be pursued: 1) Identify the essential roles that Cx43-forminghemichannels play in osteocyte responses to mechanical stress; 2) Determine if a5 integrin regulates theopening of hemichannels induced by fluid flow shear stress. The innovative and significant aspects of thisproposal are the discovery of novel mechanisms for unconventional roles of Cx43-forming hemichannels inregulating osteocyte response to mechanical strain. This study will provide comprehensive training usingbiochemical, molecular, and functional techniques combined with unique mechanical engineeringapplications.
| 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 |
