Nitric Oxide Regulates Receptor Activator of Nuclear Factor-kappaB Ligand and Osteoprotegerin Expression in Bone Marrow Stromal Cells Export

@article{citeulike:3479543, abstract = {Bone remodeling reflects an equilibrium between bone resorption and formation. The local expression of receptor activator of nuclear factor-{kappa}B 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 {micro}M) for 24 h inhibited 1,25 dihydroxyvitamin D3-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. 10.1210/en.2003-0726}, author = {Fan, Xian and Roy, Eileen and Zhu, Liping and Murphy, Tamara C. and Ackert-Bicknell, Cheryl and Hart, Michael C. and Rosen, Clifford and Nanes, Mark S. and Rubin, Janet}, citeulike-article-id = {3479543}, citeulike-linkout-0 = {http://dx.doi.org/10.1210/en.2003-0726}, citeulike-linkout-1 = {http://endo.endojournals.org/cgi/content/abstract/145/2/751}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/14563699}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=14563699}, day = {1}, doi = {10.1210/en.2003-0726}, journal = {Endocrinology}, keywords = {bone, marrow, no, opg, rankl}, month = {February}, number = {2}, pages = {751--759}, posted-at = {2008-11-04 17:24:18}, priority = {2}, title = {Nitric Oxide Regulates Receptor Activator of Nuclear Factor-{kappa}B Ligand and Osteoprotegerin Expression in Bone Marrow Stromal Cells}, url = {http://dx.doi.org/10.1210/en.2003-0726}, volume = {145}, year = {2004} }

TY - JOUR ID - citeulike:3479543 L3 - citeulike-article-id:3479543 N2 - Bone remodeling reflects an equilibrium between bone resorption and formation. The local expression of receptor activator of nuclear factor-{kappa}B 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 {micro}M) for 24 h inhibited 1,25 dihydroxyvitamin D3-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. 10.1210/en.2003-0726 IS - 2 JF - Endocrinology EP - 759 TI - Nitric Oxide Regulates Receptor Activator of Nuclear Factor-{kappa}B Ligand and Osteoprotegerin Expression in Bone Marrow Stromal Cells VL - 145 SP - 751 KW - bone KW - marrow KW - no KW - opg KW - rankl AU - Fan, Xian AU - Roy, Eileen AU - Zhu, Liping AU - Murphy, Tamara AU - Ackert-Bicknell, Cheryl AU - Hart, Michael AU - Rosen, Clifford AU - Nanes, Mark AU - Rubin, Janet PY - 2004/02/01/ UR - http://dx.doi.org/10.1210/en.2003-0726 ER -