Extracellular NAD+ metabolism modulates osteoclastogenesis

Jameel Iqbal, Mone Zaidi

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


Changes in NAD+ and its metabolites contribute to longevity and age-associated diseases. The role of NAD+ metabolism in bone diseases has however not been investigated, despite the fact that osteoporosis is a leading cause of morbidity in old age. TRAP(+) osteoclast formation from C57 Bl/6J mice was assessed after the addition of varying concentrations of NAD+ metabolites or exogenous ADPribosyl cyclase and NADase enzymes. The NAD+ metabolite cyclic ADPribose (cADPr) or exogenous addition of the enzyme ADPribosyl cyclase stimulated osteoclast formation. Blocking cADPr action with the antagonist 8-Br-cADPr potently inhibited osteoclast formation. In contrast to cADPr, its noncyclized derivative ADPribose (ADPr) or the exogenous addition of NADase both inhibited osteoclastogenesis. As CD38 is the major NAD+-degrading enzyme present in the bone marrow, these results suggest that CD38-mediated inhibition of osteoclastogenesis is related to its NADase activity, not its ADPribosyl cyclase activity.

Original languageEnglish
Pages (from-to)533-539
Number of pages7
JournalBiochemical and Biophysical Research Communications
Issue number2
StatePublished - 20 Oct 2006


  • ADPr
  • ADPribose
  • ADPribosyl cyclase
  • Cyclic ADPribose
  • Lymphocyte
  • Metabolism
  • NAD
  • NADase
  • Osteoclast
  • cADPr


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