RRC ID 42793
Author Yamamoto T, Kambe F, Cao X, Lu X, Ishiguro N, Seo H.
Title Parathyroid hormone activates phosphoinositide 3-kinase-Akt-Bad cascade in osteoblast-like cells.
Journal Bone
Abstract To understand the molecular basis underlying the anabolic action of parathyroid hormone (PTH) on bone, the anti-apoptotic action of PTH on osteoblast-like cells was investigated. Since Akt is a key protein kinase for cell survival, we focused on a possible involvement of Akt in the anti-apoptotic action of PTH. Human osteoblast-like MG-63 cells cultured without serum were treated with PTH. Western blot analysis revealed that PTH rapidly phosphorylated Akt and induced its nuclear translocation. The phosphorylation of pro-apoptotic protein Bad was also increased by PTH, leading to its inactivation. The PTH-dependent activation of Akt was also detected in other osteoblastic cell lines, SaOS-2 and ROS 17/2.8. The pretreatment of MG-63 cells with either one of inhibitors for phosphoinositide 3-kinase (PI3K), wortmannin or LY294002 prevented Akt and Bad phosphorylation. Furthermore, co-immunoprecipitation analysis revealed that PTH receptor (PTH-1R) directly interacted with p85, a regulatory subunit of PI3K, in a PTH-dependent manner. Serum withdrawal induced the apoptosis of MG-63 cells, and PTH prevented the apoptosis, which was inhibited by PI3K inhibitors. These results demonstrate the presence of a novel PTH/PTH receptor signaling cascade consisting of PTH-1R, PI3K, Akt and Bad and that this cascade can work as an anti-apoptotic signaling pathway in osteoblast-like cells.
Volume 40(2)
Pages 354-9
Published 2007-2
DOI 10.1016/j.bone.2006.09.002
PII S8756-3282(06)00693-4
PMID 17046344
MeSH Androstadienes / pharmacology Animals Apoptosis Cell Line Cell Survival Chromones / pharmacology Enzyme Activation Humans Morpholines / pharmacology Osteoblasts / physiology* Parathyroid Hormone / pharmacology Parathyroid Hormone / physiology* Peptide Fragments / pharmacology Peptide Fragments / physiology* Phosphatidylinositol 3-Kinases / metabolism* Phosphoinositide-3 Kinase Inhibitors Phosphorylation Proto-Oncogene Proteins c-akt / metabolism* Rats Receptor, Parathyroid Hormone, Type 1 / metabolism Signal Transduction Wortmannin bcl-Associated Death Protein / metabolism*
IF 4.36
Times Cited 29
Human and Animal Cells