Linked Life Data

19549171

Source:http://linkedlifedata.com/resource/pubmed/id/19549171

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2009-7-8
pubmed:abstractText
Osteoclasts are bone-resorbing cells which play an exclusive role in bone remodeling, but the molecular mechanisms of osteolysis, how osteoclasts are activated and how the lytic granules are finally released towards the bone matrix are poorly understood. Here we show that an energy molecule ATP induces osteolysis via P2X(7)-nucleotide receptor and that deacetylation of alpha-tubulin is essential for the whole process of osteolysis under the control of a tyrosine kinase Syk. By developing a traceable and reproducible in vitro analyzing system for osteoclast function, we found that ATP-signaling gives rise to two events simultaneously (i) cytoskeletal reorganization for the formation of sealing zones, ring-like adhesion structures which delimit the contact surface, and (ii) the delivery and secretion of lytic granules towards the delimited site on the matrix. We further found that deacetylation of alpha-tubulin is a critical reaction for osteoclast function. Pharmacological inhibition of alpha-tubulin deacetylation resulted in (i) failure of the sealing-zone like structure formation and (ii) ceased secretion of lytic granules. Additionally, kinetics of deacetylation was found to be regulated by Syk. These data suggest a novel P2X(7) microtubular regulation pathway related to Syk for a therapeutic target in osteolytic diseases.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1365-2443
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
14
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
871-84
pubmed:dateRevised
2011-11-2
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
ATP-induced osteoclast function: the formation of sealing-zone like structure and the secretion of lytic granules via microtubule-deacetylation under the control of Syk.
pubmed:affiliation
Division of Biochemistry, Department of Molecular and Cellular Biology, Kobe University Graduate School of Medicine, Kobe, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't