Nitric oxide mediates low magnesium inhibition of osteoblast-like cell proliferation.
An adequate intake of magnesium (Mg) is important for bone cell activity and contributes to the prevention of osteoporosis. Because (a) Mg is mitogenic for osteoblasts and (b) reduction of osteoblast proliferation is detected in osteoporosis, we investigated the influence of different concentrations of extracellular Mg on osteoblast-like SaOS-2 cell behavior. We found that low Mg inhibited SaOS-2 cell proliferation by increasing the release of nitric oxide through the up-regulation of inducible nitric oxide synthase (iNOS). Indeed, both pharmacological inhibition with the iNOS inhibitor l-N(6)-(iminoethyl)-lysine-HCl and genetic silencing of iNOS by small interfering RNA restored the normal proliferation rate of the cells. Because a moderate induction of nitric oxide is sufficient to potentiate bone resorption and a relative deficiency in osteoblast proliferation can result in their inadequate activity, we conclude that maintaining Mg homeostasis is relevant to ensure osteoblast function and, therefore, to prevent osteoporosis.
Dipartimento di Scienze Cliniche Luigi Sacco, Università di Milano, Italy.
Marzia
M
Leidi
Federica
F
Dellera
Massimo
M
Mariotti
Giuseppe
G
Banfi
Calogero
C
Crapanzano
Walter
W
Albisetti
Jeanette A M
JA
Maier
D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D006801:Humans; D008274:Magnesium / Q000008:administration & dosage*; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects*; D010024:Osteoporosis / Q000517:prevention & control; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
D034741:RNA, Small Interfering; D009569:Nitric Oxide; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; D008274:Magnesium