Linked Life Data

20392224

Source:http://linkedlifedata.com/resource/pubmed/id/20392224

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2010-4-15
pubmed:abstractText
Lrp5, the mutated gene in osteoporosis pseudoglioma (OPPG) and the high bone-mass syndrome (HBM), regulates bone formation, while beta-catenin, the molecular node of Wnt signaling, regulates bone resorption, suggesting that Lrp5 could act in a Wnt-independent manner. Using microarray and conditional gene deletion in mice, we showed that Lrp5 actually enhances bone formation by inhibiting the expression, in duodenum, of tryptophan hydroxylase 1, the rate-limiting enzyme in the serotonin biosynthetic pathway. Accordingly, serotonin circulating levels are high in Lrp5(-/-) mice and OPPG patients but low in HBM patients, and normalizing serum serotonin levels rescues the bone phenotype of the Lrp5(-/-) mice. We also showed that serotonin acts on osteoblasts through the Htr1b receptor and the transcription factor cAMP responsive element binding to inhibit their proliferation. This study shows that Lrp5 acts in gut cells, not in osteoblasts, to control bone formation via a Wnt-independent pathway and identifies a new hormone, serotonin, and a novel endocrine axis regulating bone mass. These findings may have important therapeutic implications for the treatment of low bone-mass disorders.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1749-6632
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
1192
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
103-9
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Lrp5 and bone formation : A serotonin-dependent pathway.
pubmed:affiliation
Department of Pathology, Columbia University, College of Physicians and Surgeons, New York, New York, USA.
pubmed:publicationType
Journal Article, Review, Research Support, N.I.H., Extramural