Relationship between interleukin‐1 and prostaglandins in resorbing neonatal calvaria

The relationship between the cytokine interleukin-1 and prostaglandins in resorbing bone cultures is very confusing. In some reports, the effects of interleukin-1 are described as prostaglandin dependent, but in some they appear prostaglandin independent. Recent data suggest that events occurring during the preculture period may be important for understanding later effects of any factor on bone resorption in neonatal mouse calvaria. In this study, we examined neonatal mouse calvaria morphologically for indices of resorption to determine the importance of this preculture period to their subsequent response to interleukin-1. Our results show that after a preculture period of 24 h in control media, osteoclast numbers and resorption areas are markedly enhanced. The numbers of osteoclasts fall when the calvaria are transferred to fresh control media for the following 72 h. This increase in osteoclast formation was inhibited by the addition of indomethacin (10−6 M) during the preincubation period. When interleukin-1 was added to bones after the preincubation period, osteoclast numbers present at this time were maintained and indomethacin had no effect on this response. Furthermore, the inhibitory effect of indomethacin on osteoclast formation during the preculture period could be reversed by adding prostaglandins of the E series in low concentrations together with indomethacin. The effects of interleukin-1 did not appear to be related to osteoclast precursor proliferation, since hydroxyurea (which inhibits DNA synthesis in these cultures) had no effect on the response of calvarin to interleukin-1. These results indicate that prostaglandin production by mouse calvaria increases osteoclast numbers during the preincubation period. The effects of interleukin-1 were not dependent on prostaglandin synthesis, and this factor may stimulate bone resorption by acting at later stages in osteoclast formation and activation in these bones.