Direct microsensor measurement of nitric oxide production by the osteoclast.
Nitric oxide (NO) triggers marked osteoclast retraction which closely resembles that due to Ca2+. The effect of Ca2+ has been attributed to a stimulated release of NO. Here, we show for the first time, by direct measurement with a microsensor, that osteoclasts do indeed produce NO and that this production is enhanced by a high Ca2+. We also show that the Ca2+ ionophore, A23187, mimics the latter. Furthermore, osteoclasts on dentine produce more NO than osteoclasts on glass and NO release from dentine-plated osteoclasts is much less sensitive to stimulation by Ca2+. Finally, the microsomal Ca2+ store-depleting agent, thapsigargin, attenuates NO release only from osteoclasts on glass, suggesting that stored Ca2+ has the dominant effect in modulating NO release from non-resorbing cells. NO is a powerful inhibitor of bone resorption: a direct demonstration of its production is therefore strong evidence for a role in modulating osteoclast function.
Silverton
S F
SF
School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Adebanjo
O A
OA
Moonga
B S
BS
Awumey
E M
EM
Malinski
T
T
Zaidi
M
M
D000818:Animals; D015374:Biosensing Techniques; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D002645:Chickens; D007476:Ionophores / Q000494:pharmacology; D009249:NADP / Q000494:pharmacology; D009569:Nitric Oxide / Q000032:analysis / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D010010:Osteoclasts / Q000378:metabolism*; D019284:Thapsigargin / Q000494:pharmacology
D007476:Ionophores; D009569:Nitric Oxide; D000001:Calcimycin; D009249:NADP; D019284:Thapsigargin; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D002118:Calcium