Regulation of the nuclear orphan receptor Nur77 in bone by parathyroid hormone.
Osteoblasts function under the control of several hormones and growth factors. Among them, parathyroid hormone (PTH) and steroid hormones have significant effects on bone metabolism. We show that PTH induced the expression of Nur77, a member of the NGFI-B subfamily of nuclear orphan receptors in bone. PTH rapidly and transiently induced Nur77 mRNA in primary mouse osteoblasts that peaked at 1 h and at 10 nM of hormone. Cycloheximide did not affect the induction of Nur77 mRNA, suggesting that protein synthesis is not required for the PTH effect. PTH also induced Nur77 mRNA in calvariae cultures. Finally Nur77 protein expression was induced in nuclear protein extracts of cells treated with PTH. NGFI-B nuclear receptors have been implicated in retinoic acid, vitamin D, and thyroid hormone signaling. We propose that induction of NGFI-B nuclear orphan receptors represents a potential cross-talk mechanism between PTH and steroid hormone signaling to regulate bone metabolism.
Division of Diagnostic and Surgical Sciences, School of Dentistry, University of California, Los Angeles, California 90095-1668, USA. sotirist@dent.ucla.edu
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Tetradis
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Bezouglaia
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Tsingotjidou
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Vila
D000818:Animals; D000831:Animals, Newborn; D015152:Blotting, Northern; D015153:Blotting, Western; D002478:Cells, Cultured; D046508:Culture Techniques; D003513:Cycloheximide / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D051379:Mice; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010281:Parathyroid Hormone / Q000494:pharmacology*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D012886:Skull / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
D004268:DNA-Binding Proteins; C539818:Nr4a1 protein, mouse; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D010281:Parathyroid Hormone; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D014157:Transcription Factors; D003513:Cycloheximide