Direct microsensor measurement of nitric oxide production by the osteoclast

Nitric oxide (NO) triggers marked osteoclast retraction which closely resem bles that due to Ca2+, The effect of Ca2+ has been attributed to a stimulat ed release of NO. Here, we show for the first time, by direct measurement w ith a microsensor, that osteoclasts do indeed produce NO and that this prod uction is enhanced by a high Ca2+. We also show that the Ca2+ ionophore, A2 3187, mimics the latter. Furthermore, osteoclasts on dentine produce more N O 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 osteo clasts on glass, suggesting that stored Ca2+ has the dominant effect in mod ulating NO release from non-resorbing cells. NO is a powerful inhibitor of bone resorption: a direct demonstration of its production is therefore stro ng evidence for a role in modulating osteoclast function. (C) 1999 Academic Press.