Interleukin-1 alpha induces a sustained increase in cytosolic free calcium in cultured rabbit osteoclasts.

Using laser confocal microscopy and a Ca2+ indicator, fluo-3, we find that osteoclasts respond to IL-1 alpha with a sustained increase (4 to 40 min) in cytosolic free calcium ([Ca2+]i). The delay time (T1/2) varies from 2 to 8 minutes. These effects cannot be mimicked by application of cAMP and can be blocked by removal of Ca2+ from the bathing medium. Pre-incubation with indomethacin (30 microM) does not block the IL-1 alpha effect on [Ca2+]i. We employ a 'micropipette' method and a 'pieces of cover slip' method to isolate single osteoclasts. Our results provide evidence that IL-1 alpha directly stimulates osteoclasts via a [Ca2+]i signalling pathway. We postulate that this slowly developing, long-lasting increase in [Ca2+]i in osteoclasts may account for the stimulatory effect of IL-1 alpha on osteoclastic bone resorption in conjunction with signalling molecules from osteoblasts.