Extracellular NAD+ metabolism modulates osteoclastogenesis.
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.
Iqbal
Jameel
J
Mount Sinai Bone Program, Mount Sinai School of Medicine, New york, NY 10029, USA.
Zaidi
Mone
M
D051997:ADP-ribosyl Cyclase 1 / Q000096:biosynthesis; D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D036563:Cyclic ADP-Ribose / Q000031:analogs & derivatives / Q000378:metabolism; D008214:Lymphocytes / Q000378:metabolism; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D009243:NAD / Q000378:metabolism*; D010010:Osteoclasts / Q000378:metabolism / Q000502:physiology*
C493642:8-bromo-cyclic-ADP-ribose; D009243:NAD; D036563:Cyclic ADP-Ribose; D000246:Adenosine Diphosphate Ribose; D016173:Macrophage Colony-Stimulating Factor; D051997:ADP-ribosyl Cyclase 1; D002118:Calcium