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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2007-1-12
pubmed:abstractText
The mechanisms underlying the altered osteoblastogenesis and bone loss in response to disuse are incompletely understood. Using the rat tail suspension model, we studied the effect of skeletal unloading on osteoblast and osteocyte apoptosis. Tail suspension for 2 to 7 days decreased tibial bone mass and induced early apoptotic loss of osteoblasts and delayed apoptotic loss of osteocytes. Surrenal gland weight and plasma corticosterone levels did not differ in loaded and unloaded rats at any time point, indicating that osteoblast/osteocyte apoptosis occurred independently of endogenous glucocorticoids. The mechanistic basis for the disuse-induced osteoblast/osteocyte apoptosis was examined. We found that alpha5beta1 integrin and phosphorylated phosphatidyl-inositol-3 kinase (p-PI3K) protein levels were transiently decreased in unloaded metaphyseal long bone compared to loaded bones. In contrast, p-FAK and p-ERK p42/44 levels were not significantly altered. Interestingly, the reduced p-PI3K levels in unloaded long bone was associated with decreased levels of the survival protein Bcl-2 with unaltered Bax levels, causing increased Bax/Bcl-2 levels. The results indicate that skeletal unloading in rats induces a glucocorticoid-independent, immediate increase in osteoblast apoptosis associated with decreased alpha5beta1-PI3K-Bcl-2 survival pathway in rat bone, which may contribute to the altered osteoblastogenesis and osteopenia induced by unloading.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0014-4827
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
313
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
394-403
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:17123509-Adrenal Glands, pubmed-meshheading:17123509-Animals, pubmed-meshheading:17123509-Apoptosis, pubmed-meshheading:17123509-Bone and Bones, pubmed-meshheading:17123509-Corticosterone, pubmed-meshheading:17123509-Extracellular Signal-Regulated MAP Kinases, pubmed-meshheading:17123509-Focal Adhesion Kinase 1, pubmed-meshheading:17123509-Hindlimb Suspension, pubmed-meshheading:17123509-Integrin alpha5beta1, pubmed-meshheading:17123509-Male, pubmed-meshheading:17123509-Organ Size, pubmed-meshheading:17123509-Osteoblasts, pubmed-meshheading:17123509-Phosphatidylinositol 3-Kinases, pubmed-meshheading:17123509-Proto-Oncogene Proteins c-bcl-2, pubmed-meshheading:17123509-Rats, pubmed-meshheading:17123509-Rats, Wistar, pubmed-meshheading:17123509-Signal Transduction, pubmed-meshheading:17123509-Weight-Bearing
pubmed:year
2007
pubmed:articleTitle
Skeletal unloading induces osteoblast apoptosis and targets alpha5beta1-PI3K-Bcl-2 signaling in rat bone.
pubmed:affiliation
Unit 606 INSERM, Laboratory of Osteoblast Biology and Pathology, University Paris 7, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't