In vivo administration of 1,25-dihydroxyvitamin D3 suppresses the expression of RANKL mRNA in bone of thyroparathyroidectomized rats constantly infused with PTH.

Abstract

It is known that pharmacological or toxic doses of vitamin D induce bone resorption both in vivo and in vitro, whereas physiological doses of the vitamin have a protective effect on bone in vivo. To investigate the discrepancies of the dose-dependent effect of vitamin D on bone resorption, we examined the in vivo effect of 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] on the expression of the receptor activator of nuclear factor-kappaB (NF-kappaB) ligand (RANKL) and osteoprotegerin (OPG) mRNAs in bone of thyroparathyroidectomized (TPTX) rats infused with or without parathyroid hormone (PTH). Continuous infusion of 50 ng/h of PTH greatly increased the expression of RANKL mRNA in bone of TPTX rats. Expression of OPG mRNA was not altered by PTH infusion. When graded doses of 1,25(OH)(2)D(3) was daily administered orally for 14 days to normocalcemic TPTX rats constantly infused with PTH, 0.01 and 0.1 microg/kg of 1,25(OH)(2)D(3) inhibited the PTH-induced RANKL mRNA expression, but 0.5 microg/kg of the vitamin did not inhibit it. Regulator of G protein signaling-2 (RGS-2) gene expression was suppressed by 1,25(OH)(2)D(3) dose-dependently, but PTH/PTHrP receptor mRNA expression was not altered. Bone morphometric analyses revealed that 1,25(OH)(2)D(3) suppressed PTH-induced osteoclast number in vivo. These results suggest that pharmacological or toxic doses of 1,25(OH)(2)D(3) stimulate bone resorption by inducing RANKL, but a certain range of physiological doses of the vitamin inhibit PTH-induced bone resorption, the latter mechanism appeared to be mediated, at least in part, by the suppression of the PTH/PTHrP receptor-mediated signaling.

• Authors: Yutaka Ueno, Toshimasa Shinki, Yumiko Nagai, Hisashi Murayama, Katsuyuki Fujii, Tatsuo Suda
• Journal: Journal of cellular biochemistry (J Cell Biochem) Vol. 90 Issue 2 Pg. 267-77 (Oct 01 2003) ISSN: 0730-2312 [Print] United States
• PMID: 14505343 (Publication Type: Journal Article)
• Copyright: Copyright 2003 Wiley-Liss, Inc.

Chemical References

• Calcium Channel Agonists
• Carrier Proteins
• Glycoproteins
• Ligands
• Membrane Glycoproteins
• Osteoprotegerin
• Parathyroid Hormone
• RANK Ligand
• RNA, Messenger
• Receptors, Cytoplasmic and Nuclear
• Receptors, Tumor Necrosis Factor
• Tnfrsf11b protein, rat
• Cathepsins
• Cathepsin K
• Ctsk protein, rat
• Calcitriol
• Calcium

Topics

• Animals
• Blotting, Southern
• Bone Resorption (metabolism)
• Calcification, Physiologic
• Calcitriol (administration & dosage)
• Calcium (metabolism)
• Calcium Channel Agonists (administration & dosage)
• Carrier Proteins (antagonists & inhibitors, genetics, metabolism)
• Cathepsin K
• Cathepsins (genetics, metabolism)
• Diet
• Glycoproteins (genetics, metabolism)
• Infusion Pumps
• Ligands
• Male
• Membrane Glycoproteins (antagonists & inhibitors, genetics, metabolism)
• Osteoprotegerin
• Parathyroid Hormone (administration & dosage)
• Parathyroidectomy
• Polymerase Chain Reaction
• RANK Ligand
• RNA, Messenger (metabolism)
• Rats
• Rats, Sprague-Dawley
• Receptors, Cytoplasmic and Nuclear (genetics, metabolism)
• Receptors, Tumor Necrosis Factor
• Thyroidectomy