Search

Your search keyword '"GLADU A"' showing total 2 results
Start Over Author "GLADU A" Publisher american physiological society
2 results on '"GLADU A"'

1. Induction of osteoblast differentiation indexes by PTHrP in MG-63 cells involves multiple signaling pathways

Author

CARPIO, LUISA, GLADU, JULIENNE, GOLTZMAN, DAVID, and RABBANI, SHAFAAT A.

Subjects
Osteoblasts -- Physiological aspects, Parathyroid hormone -- Physiological aspects, Peptides -- Physiological aspects, Cells -- Physiological aspects, Biological sciences
Abstract

Parathyroid hormone (PTH)-related peptide (PTHrP) can modulate the proliferation and differentiation of a number of cell types including osteoblasts. PTHrP can activate a G protein-coupled PTH/PTHrP receptor, which can interface with several second-messenger systems. In the current study, we have examined the signaling pathways involved in stimulated type I collagen and alkaline phosphatase expression in the human osteoblast-derived osteosarcoma cells, MG-63. By use of Northern blotting and histochemical analysis, maximum induction of these two markers of osteoblast differentiation occurred after 8 h of treatment with 100 nM PTHrP-(1-34). Chemical inhibitors of adenylate cyclase (H-89) or of protein kinase C (chelerythrine chloride) each diminished PTHrP-mediated type I collagen and alkaline phosphatase stimulation in a dose-dependent manner. These effects of PTHrP could also be blocked by inhibiting the Ras-mitogen-activated protein kinase (MAPK) pathway with a Ras farnesylation inhibitor, B1086, or with a MAPK inhibitor, PD-98059. Transient transfection of MG-63 cells with a mutant form of G[Alpha], which can sequester [Beta][Gamma]-subunits, showed significant downregulation of PTHrP-stimulated type I collagen expression, as did inhibition of phosphatidylinositol 3-kinase (PI 3-kinase) by wortmannin. Consequently, the [Beta][Gamma]-PI 3-kinase pathway may be involved in PTHrP stimulation of Ras. Collectively, these results demonstrate that, acting via its G protein-coupled receptor, PTHrP can induce indexes of osteoblast differentiation by utilizing multiple, perhaps parallel, signaling pathways. parathyroid hormone-related peptide; osteoblast; cell differentiation; hypercalcemia

Published
2001

2. Induction of osteoblast differentiation indexes by PTHrP in MG-63 cells involves multiple signaling pathways

Author

Luisa Carpio, David Goltzman, Shafaat A. Rabbani, and Julienne Gladu

Subjects
musculoskeletal diseases, medicine.medical_specialty, Cell type, Physiology, Endocrinology, Diabetes and Metabolism, Cellular differentiation, Parathyroid hormone, Biology, Transfection, Phosphatidylinositol 3-Kinases, Alkaloids, Physiology (medical), Internal medicine, GTP-Binding Protein alpha Subunits, Gs, Tumor Cells, Cultured, medicine, Humans, Enzyme Inhibitors, Protein Kinase C, Phosphoinositide-3 Kinase Inhibitors, Benzophenanthridines, Osteosarcoma, Sulfonamides, Osteoblasts, Parathyroid hormone-related protein, Parathyroid Hormone-Related Protein, Proteins, Cell Differentiation, Osteoblast, Blotting, Northern, Isoquinolines, Cyclic AMP-Dependent Protein Kinases, Heterotrimeric GTP-Binding Proteins, Phenanthridines, medicine.anatomical_structure, Endocrinology, Cell culture, Mutation, ras Proteins, Mitogen-Activated Protein Kinases, Signal transduction, hormones, hormone substitutes, and hormone antagonists, Signal Transduction
Abstract

Parathyroid hormone (PTH)-related peptide (PTHrP) can modulate the proliferation and differentiation of a number of cell types including osteoblasts. PTHrP can activate a G protein-coupled PTH/PTHrP receptor, which can interface with several second-messenger systems. In the current study, we have examined the signaling pathways involved in stimulated type I collagen and alkaline phosphatase expression in the human osteoblast-derived osteosarcoma cells, MG-63. By use of Northern blotting and histochemical analysis, maximum induction of these two markers of osteoblast differentiation occurred after 8 h of treatment with 100 nM PTHrP-(1-34). Chemical inhibitors of adenylate cyclase (H-89) or of protein kinase C (chelerythrine chloride) each diminished PTHrP-mediated type I collagen and alkaline phosphatase stimulation in a dose-dependent manner. These effects of PTHrP could also be blocked by inhibiting the Ras-mitogen-activated protein kinase (MAPK) pathway with a Ras farnesylation inhibitor, B1086, or with a MAPK inhibitor, PD-98059. Transient transfection of MG-63 cells with a mutant form of Galpha, which can sequester betagamma-subunits, showed significant downregulation of PTHrP-stimulated type I collagen expression, as did inhibition of phosphatidylinositol 3-kinase (PI 3-kinase) by wortmannin. Consequently, the betagamma-PI 3-kinase pathway may be involved in PTHrP stimulation of Ras. Collectively, these results demonstrate that, acting via its G protein-coupled receptor, PTHrP can induce indexes of osteoblast differentiation by utilizing multiple, perhaps parallel, signaling pathways.

Published
2001

Catalog

Books, media, physical & digital resources
See catalog results