Interleukin 1 induces multinucleation and bone-resorbing activity of osteoclasts in the absence of osteoblasts/stromal cells

Interleukin-l (IL-1) is one of the most potent bone-resorbing factors invol ved in bone loss associated with inflammation. We previously reported that IL-1 prolonged the survival of multinucleated osteoclastlike cells (OCLs) f ormed in cocultures of murine osteoblasts/stromal cells and bone marrow cel ls via the prevention of spontaneously occurring apoptosis. It was reported that macrophage colony-stimulating factor (M-CSF/CSF-1) prolongs the survi val of OCLs without the help of osteoblasts/stromal cells. The present stud y was conducted to determine whether IL-1 also directly induces the multinu cleation and activation of OCLs, Mononuclear osteoclast-like cells (prefusi on osteoclasts; pOCs) were purified using the "disintegrin'' echistatin fro m cocultures of murine osteoblastic cells (MB 1.8 cells) and bone marrow ce lls. Both IL-1 and M-CSF prolonged the survival and induced the multinuclea tion of pOCs through their respective receptors. However, actin ring format ion (a functional marker of osteoclasts) by multinucleated cells was observ ed in the pOC cultures treated with IL-1, but not those treated with M-CSF. We previously reported that enriched multinucleated OCLs as well as pOCs p laced on bone/dentine slices formed few resorption pits, but their pit-form ing activity was greatly increased by the addition of osteoblasts/stromal c ells. Here, pit-forming activity of both pOCs and enriched OCLs placed on d entine slices was induced by adding IL-1, even in the absence of osteoblast s/stromal cells, M-CSF failed to induce pit-forming activity in pOC and enr iched OCL cultures. These results indicate that IL-1 induces the multinucle ation and bone-resorbing activity of osteoclasts even in the absence of ost eoblasts/stromal cells. (C) 1999 Academic Press.