Stimulation of amphiregulin expression in osteoblastic cells by parathyroid hormone requires the protein kinase A and cAMP response element-binding protein signaling pathway

Research output: Contribution to journalArticle

Abstract

Parathyroid hormone (PTH), an anabolic agent for bone metabolism, has profound effects on gene expression in the osteoblast. Recently, we identified that amphiregulin (AR), an ECF-like ligand, is an immediate early gene for PTH treatment and has an important role in bone metabolism. In the present report, by using different PTH peptide fragments, protein kinase activators, and inhibitors, we have demonstrated that PTH regulates amphiregulin in a cAMP-protein kinase A (PKA)-dependent manner both in vitro and in vivo. We found that the phosphorylation of cAMP-response element (CRE)-binding protein (CREB) preceded AR transcription after PTH treatment. Moreover, luciferase reporter assays revealed that the binding of phosphorylated CREB to a conserved CRE site in the AR promoter plays an important role in basal, PTH-induced, and prostaglandin E2 (PGE2)-induced AR expression in osteoblastic cells. In summary, our data suggest that PTH-induced AR mRNA expression is mediated primarily through cAMP-PKA-CREB signaling.

Original languageEnglish (US)
Pages (from-to)632-640
Number of pages9
JournalJournal of Cellular Biochemistry
Volume96
Issue number3
DOIs
StatePublished - Oct 15 2005

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Cyclic AMP Response Element-Binding Protein
Cyclic AMP-Dependent Protein Kinases
Parathyroid Hormone
Metabolism
Carrier Proteins
Bone
Anabolic Agents
Phosphorylation
Peptide Fragments
Osteoblasts
Bone and Bones
Response Elements
Transcription
Protein Kinase Inhibitors
Immediate-Early Genes
Luciferases
Dinoprostone
Gene expression
Amphiregulin
Assays

Keywords

  • Amphiregulin
  • cAMP response element-binding protein (CREB)
  • Osteoblastic cells
  • Parathyroid hormone
  • Protein kinase A

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

Cite this

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title = "Stimulation of amphiregulin expression in osteoblastic cells by parathyroid hormone requires the protein kinase A and cAMP response element-binding protein signaling pathway",
abstract = "Parathyroid hormone (PTH), an anabolic agent for bone metabolism, has profound effects on gene expression in the osteoblast. Recently, we identified that amphiregulin (AR), an ECF-like ligand, is an immediate early gene for PTH treatment and has an important role in bone metabolism. In the present report, by using different PTH peptide fragments, protein kinase activators, and inhibitors, we have demonstrated that PTH regulates amphiregulin in a cAMP-protein kinase A (PKA)-dependent manner both in vitro and in vivo. We found that the phosphorylation of cAMP-response element (CRE)-binding protein (CREB) preceded AR transcription after PTH treatment. Moreover, luciferase reporter assays revealed that the binding of phosphorylated CREB to a conserved CRE site in the AR promoter plays an important role in basal, PTH-induced, and prostaglandin E2 (PGE2)-induced AR expression in osteoblastic cells. In summary, our data suggest that PTH-induced AR mRNA expression is mediated primarily through cAMP-PKA-CREB signaling.",
keywords = "Amphiregulin, cAMP response element-binding protein (CREB), Osteoblastic cells, Parathyroid hormone, Protein kinase A",
author = "Ling Qin and Nicola Partridge",
year = "2005",
month = "10",
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doi = "10.1002/jcb.20550",
language = "English (US)",
volume = "96",
pages = "632--640",
journal = "Journal of Cellular Biochemistry",
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T1 - Stimulation of amphiregulin expression in osteoblastic cells by parathyroid hormone requires the protein kinase A and cAMP response element-binding protein signaling pathway

AU - Qin, Ling

AU - Partridge, Nicola

PY - 2005/10/15

Y1 - 2005/10/15

N2 - Parathyroid hormone (PTH), an anabolic agent for bone metabolism, has profound effects on gene expression in the osteoblast. Recently, we identified that amphiregulin (AR), an ECF-like ligand, is an immediate early gene for PTH treatment and has an important role in bone metabolism. In the present report, by using different PTH peptide fragments, protein kinase activators, and inhibitors, we have demonstrated that PTH regulates amphiregulin in a cAMP-protein kinase A (PKA)-dependent manner both in vitro and in vivo. We found that the phosphorylation of cAMP-response element (CRE)-binding protein (CREB) preceded AR transcription after PTH treatment. Moreover, luciferase reporter assays revealed that the binding of phosphorylated CREB to a conserved CRE site in the AR promoter plays an important role in basal, PTH-induced, and prostaglandin E2 (PGE2)-induced AR expression in osteoblastic cells. In summary, our data suggest that PTH-induced AR mRNA expression is mediated primarily through cAMP-PKA-CREB signaling.

AB - Parathyroid hormone (PTH), an anabolic agent for bone metabolism, has profound effects on gene expression in the osteoblast. Recently, we identified that amphiregulin (AR), an ECF-like ligand, is an immediate early gene for PTH treatment and has an important role in bone metabolism. In the present report, by using different PTH peptide fragments, protein kinase activators, and inhibitors, we have demonstrated that PTH regulates amphiregulin in a cAMP-protein kinase A (PKA)-dependent manner both in vitro and in vivo. We found that the phosphorylation of cAMP-response element (CRE)-binding protein (CREB) preceded AR transcription after PTH treatment. Moreover, luciferase reporter assays revealed that the binding of phosphorylated CREB to a conserved CRE site in the AR promoter plays an important role in basal, PTH-induced, and prostaglandin E2 (PGE2)-induced AR expression in osteoblastic cells. In summary, our data suggest that PTH-induced AR mRNA expression is mediated primarily through cAMP-PKA-CREB signaling.

KW - Amphiregulin

KW - cAMP response element-binding protein (CREB)

KW - Osteoblastic cells

KW - Parathyroid hormone

KW - Protein kinase A

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