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Parathyroid hormone and parathyroid hormone-related protein exert both pro- and anti-apoptotic effects in mesenchymal cells.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 2002 May 31; Vol. 277 (22), pp. 19374-81. Date of Electronic Publication: 2002 Mar 15. - Publication Year :
- 2002
-
Abstract
- During bone formation, multipotential mesenchymal cells proliferate and differentiate into osteoblasts, and subsequently many die because of apoptosis. Evidence suggests that the receptor for parathyroid hormone (PTH) and parathyroid hormone-related protein (PTHrP), the PTH-1 receptor (PTH-1R), plays an important role in this process. Multipotential mesenchymal cells (C3H10T1/2) transfected with normal or mutant PTH-1Rs and MC3T3-E1 osteoblastic cells were used to explore the roles of PTH, PTHrP, and the PTH-1R in cell viability relative to osteoblastic differentiation. Overexpression of wild-type PTH-1R increased cell numbers and promoted osteocalcin gene expression versus inactivated mutant receptors. Furthermore, the effects of PTH and PTHrP on apoptosis were dramatically dependent on cell status. In preconfluent C3H10T1/2 and MC3T3-E1 cells, PTH and PTHrP protected against dexamethasone-induced reduction in cell viability, which was dependent on cAMP activation. Conversely, PTH and PTHrP resulted in reduced cell viability in postconfluent cells, which was also dependent on cAMP activation. Further, the proapoptotic-like effects were associated with an inhibition of Akt phosphorylation. These data suggest that parathyroid hormones accelerate turnover of osteoblasts by promoting cell viability early and promoting cell departure from the differentiation program later in their developmental scheme. Both of these actions occur at least in part via the protein kinase A pathway.
- Subjects :
- 3T3 Cells
Adenylyl Cyclases metabolism
Animals
Blotting, Northern
Blotting, Western
Cell Line
Cell Survival
Cloning, Molecular
Cyclic AMP metabolism
Cyclic AMP-Dependent Protein Kinases metabolism
Dexamethasone pharmacology
Enzyme-Linked Immunosorbent Assay
Mesoderm metabolism
Mice
Mice, Inbred C3H
Osteocalcin biosynthesis
Osteocalcin metabolism
Parathyroid Hormone-Related Protein
Phosphorylation
Plasmids metabolism
Protein Binding
Proto-Oncogene Proteins metabolism
Proto-Oncogene Proteins c-akt
Receptors, Parathyroid Hormone metabolism
Receptors, Parathyroid Hormone physiology
Time Factors
Transfection
Apoptosis
Mesoderm cytology
Parathyroid Hormone physiology
Protein Serine-Threonine Kinases
Proteins physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0021-9258
- Volume :
- 277
- Issue :
- 22
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 11897779
- Full Text :
- https://doi.org/10.1074/jbc.M108913200