Lipopolysaccharide supports survival and fusion of preosteoclasts independent of TNF-alpha, IL-1, and RANKL

Lipopolysaccharide (LPS), a cell component of Gram-negative bacteria, is a pathogen of inflammatory bone loss. To examine the effects of LPS on the su rvival and fusion of osteoclasts, mononuclear osteoclasts (preosteoclasts, pOCs) were collected from a mouse co-culture system and cultured in the pre sence or absence of LPS. Most pOCs died within 24 h in the absence of any s timulus. LPS as well as receptor activator of NF-kappaB ligand (RANKL) supp orted the survival of pOCs, and induced their fusion to form multinucleated cells (MNCs). Like authentic osteoclasts, MNCs induced by LPS expressed ca lcitonin receptors, and formed actin rings on culture plates. LPS-induced M NC formation in pOC cultures was observed even in the presence of osteoprot egerin and interleukin (IL)-1-receptor antagonists. MNC formation was also stimulated by LPS in pOC cultures prepared from tumor necrosis factor (TNF) -receptor-1 or TNF-receptor-II deficient mice. LPS induced the degradation of I kappaB in pOCs within 20 min. Lactacystin, an inhibitor of NF-kappaB a ctivation, and wortmannin, an inhibitor of phosphatidylinositol-3 kinase, s trongly inhibited LPS-induced MNC formation in pOC cultures. LPS induced pi t-forming activity of pOCs in the presence of macrophage-colony stimulating factor (M-CSF). These findings suggest that LPS stimulates the survival an d fusion of pOCs, independent of RANKL, IL-1 or TNF-alpha action. Activatio n of NF-kappaB and phosphatidylinositol-3 kinase appeared to be involved in LPS-induced effects on pOCs. These observations suggest that LPS is involv ed directly in inflammatory bone loss, and also indirectly through the prod uction of LPS-induced host factors such as IL-1 and TNF-alpha. (C) 2002 Wil ey-Liss, Inc.