| RRC ID |
1356
|
| 著者 |
Fan X, Roy E, Zhu L, Murphy TC, Ackert-Bicknell C, Hart CM, Rosen C, Nanes MS, Rubin J.
|
| タイトル |
Nitric oxide regulates receptor activator of nuclear factor-kappaB ligand and osteoprotegerin expression in bone marrow stromal cells.
|
| ジャーナル |
Endocrinology
|
| Abstract |
Bone remodeling reflects an equilibrium between bone resorption and formation. The local expression of receptor activator of nuclear factor-kappaB ligand (RANKL) and osteoprotegerin (OPG) in bone determines the entry of monoblastic precursors into the osteoclast lineage and subsequent bone resorption. Nitric oxide (NO) inhibits osteoclastic bone resorption in vitro and regulates bone remodeling in vivo. An interaction of NO with RANKL and OPG has not been studied. Here, we show that treatment of ST-2 murine stromal cells with the NO donor sodium nitroprusside (100 microm) for 24 h inhibited 1,25 dihydroxyvitamin D(3)-induced RANKL mRNA to less than 33 +/- 7% of control level, whereas OPG mRNA increased to 204 +/- 19% of control. NOR-4 replicated these NO effects. The effects of NO were dose dependent and associated with changes in protein levels: RANKL protein decreased and OPG protein increased after treatment with NO. PTH-induced RANKL expression in primary stromal cells was inhibited by sodium nitroprusside, indicating that the NO effect did not require vitamin D. NO donor did not change the stability of RANKL or OPG mRNAs, suggesting that NO affected transcription. Finally, cGMP, which can function as a second messenger for NO, did not reproduce the NO effect, nor did inhibition of endogenous guanylate cyclase prevent the NO effect on these osteoactive genes. The effect of NO to decrease the RANKL/OPG equilibrium should lead to decreased recruitment of osteoclasts and positive bone formation. Thus, drugs and conditions that cause local increase in NO formation in bone may have positive effects on bone remodeling.
|
| 巻・号 |
145(2)
|
| ページ |
751-9
|
| 公開日 |
2004-2-1
|
| DOI |
10.1210/en.2003-0726
|
| PII |
en.2003-0726
|
| PMID |
14563699
|
| MeSH |
Animals
Bone Marrow Cells / metabolism*
Calcitriol / pharmacology
Carrier Proteins / genetics*
Cell Line
Cyclic GMP / pharmacology
Enzyme Inhibitors / pharmacology
Gene Expression Regulation / drug effects*
Glycoproteins / genetics*
Guanylate Cyclase / antagonists & inhibitors
Male
Membrane Glycoproteins / genetics*
Mice
Mice, Inbred C57BL
Nitric Oxide / pharmacology*
Nitric Oxide Donors / pharmacology
Nitroprusside / pharmacology
Osteoprotegerin
Parathyroid Hormone / pharmacology
RANK Ligand
RNA, Messenger / analysis
Receptor Activator of Nuclear Factor-kappa B
Receptors, Cytoplasmic and Nuclear / genetics*
Receptors, Tumor Necrosis Factor
Stromal Cells / metabolism*
Transcription, Genetic / drug effects
|
| IF |
3.934
|
| 引用数 |
75
|
|
WOS 分野
|
ENDOCRINOLOGY & METABOLISM
|
| リソース情報 |
| ヒト・動物細胞 |
ST2(RCB0224) |
