Source:http://linkedlifedata.com/resource/pubmed/id/21325041
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
5
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| pubmed:dateCreated |
2011-4-22
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| pubmed:abstractText |
The rate of endochondral bone growth determines final height in humans and is tightly controlled. Glycogen synthase kinase-3 (GSK-3) is a negative regulator of several signaling pathways that govern bone growth, such as insulin/IGF and Wnt/?-catenin. The two GSK-3 proteins, GSK-3? and GSK-3?, display both overlapping and distinct roles in different tissues. Here we show that pharmacological inhibition of GSK-3 signaling in a mouse tibia organ culture system results in enhanced bone growth, accompanied by increased proliferation of growth plate chondrocytes and faster turnover of hypertrophic cartilage to bone. GSK-3 inhibition rescues some, but not all, effects of phosphatidylinositide 3-kinase inhibition in this system, in agreement with the antagonistic role of these two kinases in response to signals such as IGF. However, cartilage-specific deletion of the Gsk3b gene in mice has minimal effects on skeletal growth or development. Molecular analyses demonstrated that compensatory up-regulation of GSK-3? protein levels in cartilage is the likely cause for this lack of effect. To our knowledge, this is the first tissue in which such a compensatory mechanism is described. Thus, our study provides important new insights into both skeletal development and the biology of GSK-3 proteins.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
AIM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/3-(3-chloro-4-hydroxyphenylamino)-4-...,
http://linkedlifedata.com/resource/pubmed/chemical/Aminophenols,
http://linkedlifedata.com/resource/pubmed/chemical/Glycogen Synthase Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Maleimides,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/beta Catenin,
http://linkedlifedata.com/resource/pubmed/chemical/glycogen synthase kinase 3 alpha,
http://linkedlifedata.com/resource/pubmed/chemical/glycogen synthase kinase 3 beta
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| pubmed:status |
MEDLINE
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| pubmed:month |
May
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| pubmed:issn |
1945-7170
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:volume |
152
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
1755-66
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| pubmed:dateRevised |
2011-11-2
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| pubmed:meshHeading |
pubmed-meshheading:21325041-Aminophenols,
pubmed-meshheading:21325041-Animals,
pubmed-meshheading:21325041-Blotting, Western,
pubmed-meshheading:21325041-Cartilage,
pubmed-meshheading:21325041-Cell Proliferation,
pubmed-meshheading:21325041-Chondrocytes,
pubmed-meshheading:21325041-Female,
pubmed-meshheading:21325041-Gene Deletion,
pubmed-meshheading:21325041-Glycogen Synthase Kinase 3,
pubmed-meshheading:21325041-Growth Plate,
pubmed-meshheading:21325041-Immunohistochemistry,
pubmed-meshheading:21325041-Male,
pubmed-meshheading:21325041-Maleimides,
pubmed-meshheading:21325041-Mice,
pubmed-meshheading:21325041-Mice, Knockout,
pubmed-meshheading:21325041-Organ Culture Techniques,
pubmed-meshheading:21325041-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:21325041-Tibia,
pubmed-meshheading:21325041-Up-Regulation,
pubmed-meshheading:21325041-beta Catenin
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| pubmed:year |
2011
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| pubmed:articleTitle |
Deletion of glycogen synthase kinase-3? in cartilage results in up-regulation of glycogen synthase kinase-3? protein expression.
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| pubmed:affiliation |
Department of Physiology and Pharmacology, University of Western Ontario, London, Ontario, Canada. fbeier@uwo.ca
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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