Stimulation of amphiregulin expression in osteoblastic cells by parathyroid hormone requires the protein kinase A and cAMP response element-binding protein signaling pathway.
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 EGF-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.
Qin
Ling
L
Department of Physiology and Biophysics, UMDNJ-Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA.
Partridge
Nicola C
NC
D066258:Amphiregulin; D000818:Animals; D001483:Base Sequence; D001842:Bone and Bones / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism; D066255:EGF Family of Proteins; D005786:Gene Expression Regulation; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D010006:Osteoblasts / Q000166:cytology / Q000502:physiology*; D010281:Parathyroid Hormone / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D051381:Rats; D017207:Rats, Sprague-Dawley; D016415:Sequence Alignment; D015398:Signal Transduction / Q000502:physiology*
C587848:AREG protein, human; D066258:Amphiregulin; C587849:Areg protein, mouse; C587850:Areg protein, rat; D017362:Cyclic AMP Response Element-Binding Protein; D066255:EGF Family of Proteins; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D010281:Parathyroid Hormone; D017868:Cyclic AMP-Dependent Protein Kinases; D015232:Dinoprostone