Parathyroid hormone induces the nuclear orphan receptor NOR-1 in osteoblasts.
Parathyroid hormone (PTH) significantly affects osteoblast function by altering gene expression. We have identified neuron-derived orphan receptor-1 (NOR-1) as a PTH-induced primary gene in osteoblastic cells. NOR-1, Nurr1, and Nur77 comprise the NGFI-B nuclear orphan receptor family and Nurr1 and Nur77 are PTH-induced primary osteoblastic genes. Ten nM PTH maximally induced NOR-1 mRNA at 2h in primary mouse osteoblasts and at 1h in mouse calvariae. Cycloheximide pretreatment did not inhibit PTH-induced NOR-1 mRNA. PTH activates cAMP-protein kinase A (PKA), protein kinase C (PKC), and calcium signaling. Forskolin (PKA activator) and PMA (PKC activator) mimicked PTH-induced NOR-1 mRNA. Ionomycin (calcium ionophore) and PTH(3-34), which do not activate PKA, failed to induce NOR-1 mRNA. PKA inhibition with H89 blocked PTH- and FSK-induced NOR-1 mRNA. PMA pretreatment to deplete PKC inhibited PMA-induced, but not PTH-induced, NOR-1 mRNA. We conclude that NOR-1 is a PTH-regulated primary osteoblastic gene that is induced mainly through cAMP-PKA signaling.
Pirih
Flavia Q
FQ
Division of Diagnostic and Surgical Sciences, UCLA School of Dentistry, Los Angeles, CA 90095-1668, USA.
Nervina
Jeanne M
JM
Pham
Lee
L
Aghaloo
Tara
T
Tetradis
Sotirios
S
D016475:3T3 Cells; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D007700:Kinetics; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000008:administration & dosage / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics*; D011987:Receptors, Steroid; D011988:Receptors, Thyroid Hormone; D015398:Signal Transduction / Q000187:drug effects; D012886:Skull / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D009419:Nerve Tissue Proteins; C490411:Nr4a3 protein, mouse; D010281:Parathyroid Hormone; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D011987:Receptors, Steroid; D011988:Receptors, Thyroid Hormone; D003513:Cycloheximide; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C