Bone (New York, N.Y.), 2013-07, Vol.55 (1), p.126-131
2013
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Details
- Autor(en) / Beteiligte
- Titel
- PTEN regulation by the Akt/GSK-3β axis during RANKL signaling
- Ist Teil von
- Bone (New York, N.Y.), 2013-07, Vol.55 (1), p.126-131
- Ort / Verlag
- Amsterdam: Elsevier Inc
- Erscheinungsjahr
- 2013
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Abstract Phosphatase and tensin homolog (PTEN) negatively regulates phosphoinositide 3-kinase (PI3K)/Akt signaling as a lipid phosphatase for the second messenger phosphatidylinositol 3,4,5-triphosphate. We discovered recently that inactivating glycogen synthase kinase-3β (GSK-3β) via Akt plays an important role in receptor activator of nuclear factor κb ligand (RANKL)-induced osteoclastogenesis. However, the signaling link between GSK-3β and PTEN in RANKL signaling has not been revealed. Downregulating PTEN by RNA interference increases Akt and GSK-3β phosphorylation levels by RANKL, thereby promoting the formation of osteoclasts. PTEN phosphorylation at threonine 366 (T366) decreased gradually during RANKL-induced osteoclastogenesis, whereas PTEN protein levels were unaffected. Interestingly, the PTEN phosphorylation defective mutant (T366A) showed increased osteoclastogenesis, which is consistent with its lower phosphatase activity, compared to that of wild-type PTEN. Moreover, treatment with the GSK-3 inhibitor SB216763 suppressed PTEN phosphorylation levels and phosphatase activity and enhanced Akt phosphorylation. These data suggest that inhibiting GSK-3β during RANKL-induced osteoclastogenesis decreases PTEN phosphorylation, leading to enhanced osteoclast differentiation through Akt activation.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 8756-3282eISSN: 1873-2763DOI: 10.1016/j.bone.2013.02.005Titel-ID: cdi_proquest_miscellaneous_1627986988
- Format
- –
- Schlagworte
- Akt, Animals, Biological and medical sciences, Cell Differentiation, Down-Regulation, Fundamental and applied biological sciences. Psychology, Glycogen Synthase Kinase 3 - antagonists & inhibitors, Glycogen Synthase Kinase 3 - metabolism, Glycogen Synthase Kinase 3 beta, GSK-3β, Mice, Mice, Inbred C57BL, Models, Biological, Mutant Proteins - metabolism, Orthopedics, Osteoclastogenesis, Osteoclasts - cytology, Osteoclasts - enzymology, Osteogenesis, Phosphorylation, Proto-Oncogene Proteins c-akt - metabolism, PTEN, PTEN Phosphohydrolase - deficiency, PTEN Phosphohydrolase - metabolism, RANK Ligand - metabolism, RANKL, Signal Transduction, Vertebrates: anatomy and physiology, studies on body, several organs or systems