Linked Life Data

19096040

Source:http://linkedlifedata.com/resource/pubmed/id/19096040

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2009-5-20
pubmed:abstractText
Mesenchymal stem cells within the bone are responsible for the generation of osteoblasts, chondrocytes, and adipocytes. In rodents, Indian hedgehog has been shown to play a role in osteoblast differentiation. However, evidence for a direct function of hedgehog (Hh) in human osteoblastic differentiation is missing. Using different models of human mesenchymal stem cells we show that Hh signaling decreases during osteoblast differentiation. This is associated with a decrease in Smoothened expression, a key partner that triggers Hh signaling, and in the number of cells displaying a primary cilium, an organelle necessary for Hh signaling. Remarkably, treatment of human mesenchymal stem cells with sonic hedgehog or two molecules able to activate Hh signaling inhibits osteoblast differentiation. This inhibition is visualized through a decrease in mineralization and in the expression of osteoblastic genes. In particular, activation of Hh signaling induces a decrease in Runx2 expression, a key transcriptional factor controlling the early stage of osteoblast differentiation. Consistently, the activation of Hh signaling during the first days of differentiation is sufficient to inhibit osteoblast differentiation, whereas differentiated osteoblasts are not affected by Hh signaling. In summary, we show here, using various inducers of Hh signaling and mesenchymal stem cells of two different origins, that Hh signaling inhibits human osteoblast differentiation, in sharp contrast to what has been described in rodent cells. This species difference should be taken into account for screening for pro-osteogenic molecules.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1549-4918
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
27
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
703-13
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Activation of hedgehog signaling inhibits osteoblast differentiation of human mesenchymal stem cells.
pubmed:affiliation
Institute of Signaling, Biology, Development and Cancer, Université de Nice Sophia-Antipolis, CNRS UMR, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't