Nicorandil inhibits osteoclast differentiation in vitro.
Nicorandil is a hybrid angina therapeutic agent that has nitric oxide (NO) action and the ability to open ATP-sensitive K+channels (KATPchannels). A transient increase in NO and intracellular Ca2+has been demonstrated to be highly involved in the differentiation and activation of osteoclasts. The objective of this study was to verify that the pharmacological effect of nicorandil suppresses the differentiation process of osteoclasts in vitro. Although little authentic NO production was detected in the culture medium in osteoclast formation assays, NO production increased only in the presence of nicorandil. The number of osteoclasts decreased markedly at late time-points after nicorandil addition compared with the number at early time-points. Both the number of TRAP-positive multinucleated cells and the number of cells that obtained F-actin rings decreased in the presence of nicorandil in a concentration-dependent manner. The osteo assay showed that the bone resorption area was also reduced with nicorandil in a concentration-dependent manner. An inhibition recovery experiment was conducted by adding a soluble guanylyl cyclase (sGC) inhibitor (ODQ) and a KATPchannel-opening inhibitor (glibenclamide) during the osteoclast formation process. In the inhibition recovery experiment, the inhibitory effect of nicorandil on osteoclastogenesis was blocked by the addition of ODQ and glibenclamide. These results suggest that both the NO and KATPchannel-opening activity of nicorandil inhibit osteoclast differentiation. Further study of nicorandil may lead to the development of drugs for osteoporosis treatment.
Department of Pharmacology, Osaka Dental University, -1, Kuzuhahanazono-cho, Hirakata-shi 573-1121, Japan. Electronic address: g-iwaki@nmc-kobe.org.
Futoshi
F
Iwaki
Department of Pharmacology, Osaka Dental University, -1, Kuzuhahanazono-cho, Hirakata-shi 573-1121, Japan. Electronic address: amano@cc.osaka-dent.ac.jp.
Hitoshi
H
Amano
Department of Pharmacology, Osaka Dental University, -1, Kuzuhahanazono-cho, Hirakata-shi 573-1121, Japan. Electronic address: ohura@cc.osaka-dent.ac.jp.
Kiyoshi
K
Ohura
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D054086:KATP Channels / Q000037:antagonists & inhibitors; D051379:Mice; D020108:Nicorandil / Q000494:pharmacology*; D009569:Nitric Oxide / Q000096:biosynthesis; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D010069:Oxadiazoles / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D000071756:Soluble Guanylyl Cyclase / Q000037:antagonists & inhibitors
C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D054086:KATP Channels; D010069:Oxadiazoles; D011810:Quinoxalines; D020108:Nicorandil; D009569:Nitric Oxide; D000071756:Soluble Guanylyl Cyclase
Nicorandil; Osteoporosis; Suppression of osteoclast differentiation