Lymphoblastoid interferon-alpha downregulates parathyroid hormone (PTH)/PTH-related peptide (PTHrP) receptor expression in human osteoblastic cells (Saos-2). 1998

E Tsuda-Futami, and A Shioi, and S Jono, and M Inaba, and Y Nishizawa, and H Morii
Second Department of Internal Medicine, Osaka City University Medical School, Osaka, Japan.

Interferon-alpha (IFN-alpha) is a pleiotropic cytokine that modulates the cellular functions of both osteoblastic and osteoclastic lineages. It remains unclear whether IFN-alpha regulates the expression of parathyroid hormone (PTH)/PTH-related peptide (PTHrP) receptor, which is a major target molecule regulating skeletal metabolism. In this study, we examined the effect of IFN-alpha on the expression of PTH/PTHrP receptor in human osteoblastic cells (Saos-2). IFN-alpha inhibited the expression of PTH/PTHrP receptor gene in both a time- and dose-dependent manner. The mRNA level was decreased to 61.1% of that of the untreated control by 48 h treatment with 6000 U/mL of IFN-alpha. IFN-alpha also decreased cAMP response to PTH(1-34) in a dose-dependent manner and significantly depressed expression of the receptor protein. However, IFN-alpha did not exert any effect on other osteoblastic markers, such as alkaline phosphatase (ALP) activity, cAMP response to prostaglandin E2 (PGE2), and secretion of bone gla-protein (BGP) and bone sialoprotein (BSP). Finally, IFN-alpha decreased PTH/PTHrP receptor mRNA to 60.7% that of control in the presence of actinomycin D. These data suggest that IFN-alpha downregulates the expression of PTH/PTHrP receptor and its signaling without affecting other osteoblastic markers, and that IFN-alpha regulates its gene expression mainly by decreasing the stability of its mRNA.

UI MeSH Term Description Entries
D010006 Osteoblasts Bone-forming cells which secrete an EXTRACELLULAR MATRIX. HYDROXYAPATITE crystals are then deposited into the matrix to form bone. Osteoblast
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000242 Cyclic AMP An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH. Adenosine Cyclic 3',5'-Monophosphate,Adenosine Cyclic 3,5 Monophosphate,Adenosine Cyclic Monophosphate,Adenosine Cyclic-3',5'-Monophosphate,Cyclic AMP, (R)-Isomer,Cyclic AMP, Disodium Salt,Cyclic AMP, Monoammonium Salt,Cyclic AMP, Monopotassium Salt,Cyclic AMP, Monosodium Salt,Cyclic AMP, Sodium Salt,3',5'-Monophosphate, Adenosine Cyclic,AMP, Cyclic,Adenosine Cyclic 3',5' Monophosphate,Cyclic 3',5'-Monophosphate, Adenosine,Cyclic Monophosphate, Adenosine,Cyclic-3',5'-Monophosphate, Adenosine,Monophosphate, Adenosine Cyclic
D000469 Alkaline Phosphatase An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. EC 3.1.3.1.
D012333 RNA, Messenger RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm. Messenger RNA,Messenger RNA, Polyadenylated,Poly(A) Tail,Poly(A)+ RNA,Poly(A)+ mRNA,RNA, Messenger, Polyadenylated,RNA, Polyadenylated,mRNA,mRNA, Non-Polyadenylated,mRNA, Polyadenylated,Non-Polyadenylated mRNA,Poly(A) RNA,Polyadenylated mRNA,Non Polyadenylated mRNA,Polyadenylated Messenger RNA,Polyadenylated RNA,RNA, Polyadenylated Messenger,mRNA, Non Polyadenylated
D012795 Sialoglycoproteins Glycoproteins which contain sialic acid as one of their carbohydrates. They are often found on or in the cell or tissue membranes and participate in a variety of biological activities. Polysialoglycoprotein,Sialoglycopeptide,Sialoglycopeptides,Sialoglycoprotein,Sialoprotein,Sialoproteins,Polysialoglycoproteins
D015232 Dinoprostone The most common and most biologically active of the mammalian prostaglandins. It exhibits most biological activities characteristic of prostaglandins and has been used extensively as an oxytocic agent. The compound also displays a protective effect on the intestinal mucosa. PGE2,PGE2alpha,Prostaglandin E2,Prostaglandin E2alpha,PGE2 alpha,Prepidil Gel,Prostaglandin E2 alpha,Prostenon,E2 alpha, Prostaglandin,E2, Prostaglandin,E2alpha, Prostaglandin,Gel, Prepidil,alpha, PGE2,alpha, Prostaglandin E2
D015536 Down-Regulation A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins. Receptor Down-Regulation,Down-Regulation (Physiology),Downregulation,Down Regulation,Down-Regulation, Receptor
D015675 Osteocalcin Vitamin K-dependent calcium-binding protein synthesized by OSTEOBLASTS and found primarily in BONES. Serum osteocalcin measurements provide a noninvasive specific marker of bone metabolism. The protein contains three residues of the amino acid gamma-carboxyglutamic acid (Gla), which, in the presence of CALCIUM, promotes binding to HYDROXYAPATITE and subsequent accumulation in BONE MATRIX. Bone Gla Protein,Calcium-Binding Protein, Vitamin K-Dependent,Gla Protein, Bone,Vitamin K-Dependent Bone Protein,4-Carboxyglutamic Protein, Bone,Bone gamma-Carboxyglutamic Acid Protein,4 Carboxyglutamic Protein, Bone,Bone 4-Carboxyglutamic Protein,Bone gamma Carboxyglutamic Acid Protein,Calcium Binding Protein, Vitamin K Dependent,Protein, Bone 4-Carboxyglutamic,Protein, Bone Gla,Vitamin K Dependent Bone Protein

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