Activation of osteoclasts by interleukin-1: divergent responsiveness in osteoclasts formed in vivo and in vitro

Recently, it has been found that osteoclasts are induced and activated by osteoblastic cells through expression of receptor activator NF-kB ligand (RANKL), and that soluble recombinant RANKL, with M-CSF, can replace the need for osteoblastic cells in osteoclast formation. We exploited this opportunity to compare the responsiveness of osteoclast-like cells (OCL) formed in vitro in the absence of osteoblasts, with that of osteoclasts ex vivo. We found that while OCL responded to several hormones and cytokines like ex vivo osteoclasts, their responsiveness to interleukin-1 (IL-1) was fundamentally different: IL1 directly stimulated actin ring formation in OCL, but had no effect on actin rings or survival in osteoclasts ex vivo unless osteoblastic cells were present. This difference could not be attributed to the use of plastic culture substrates for OCL formation, nor to osteoblastic contamination, and did not seem to be mediated by the macrophages that form in OCL cultures. To understand the mechanisms by which IL-1 induces bone loss, it will need to be determined whether or not IL-1-responsive OCLs have a counterpart in vivo. Whichever is the case, our data suggest that the behavior of osteoclasts formed in culture will not always predict that of osteoclasts in vivo.