Low NO concentrations inhibit osteoclast formation in mouse marrow cultures by cGMP-dependent mechanism

L. Shannon Holliday, Alan D. Dean, Royana H. Lin, James E. Greenwald, Stephen L. Gluck

Research output: Contribution to journalArticlepeer-review

50 Scopus citations


High concentrations of nitric oxide (NO) inhibit bone resorption by mature osteoclasts. We examined the effects of low NO concentrations on osteoclast formation in mouse bone marrow cultures. The NO releasers sodium nitroprusside (SNP) and S-nitroso-N-acetyl-DL-penicillamine inhibited the formation of multinucleated cells expressing tartrate-resistant acid phosphatase (a marker for osteoclasts) when administered during the last 3 days of 6-day cultures (differentiation stage) but not during the first 3 days (proliferation stage). SNP (1 μM) completely inhibited pit formation on dentine wafers when added to cultures during osteoclast formation, but 100 μM SNP was required to inhibit pitting by mature osteoclasts. Conversely, the NO synthase inhibitors aminoguanidine and nitro-L-arginine methyl ester both increased osteoclast formation. Inhibition of osteoclast formation by NO likely was guanosine 3',5'-cyclic monophosphate (cGMP) dependent, as SNP increased cGMP in marrow cultures, and 1 mM 8-bromo-cGMP or dibutyryl-cGMP reduced osteoclast formation when administered during the differentiation stage. The cGMP-specific type V phosphodiesterase inhibitor, zaprinast (M and B 22948) also inhibited osteoclast formation (half-mammal inhibitory constant, 100 pM) only when added during the differentiation stage. We conclude that the differentiation stage of osteoclast formation is inhibited by increases in cGMP levels elicited by NO.

Original languageEnglish (US)
Pages (from-to)F283-F291
JournalAmerican Journal of Physiology - Renal Physiology
Issue number3 41-3
StatePublished - Mar 1997


  • Bone remodeling
  • Guanosine 3',5'-cyclic monophosphate
  • Guanylyl cyclase
  • Nitric oxide
  • Osteoporosis
  • Phosphodiesterase V
  • Zaprinast

ASJC Scopus subject areas

  • Physiology
  • Urology


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