| First Author | Gillespie JR | Year | 2011 |
| Journal | Endocrinology | Volume | 152 |
| Issue | 5 | Pages | 1755-66 |
| PubMed ID | 21325041 | Mgi Jnum | J:173862 |
| Mgi Id | MGI:5050462 | Doi | 10.1210/en.2010-1412 |
| Citation | Gillespie JR, et al. (2011) Deletion of glycogen synthase kinase-3beta in cartilage results in up-regulation of glycogen synthase kinase-3alpha protein expression. Endocrinology 152(5):1755-66 |
| 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/beta-catenin. The two GSK-3 proteins, GSK-3alpha and GSK-3beta, 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-3alpha 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. |
