GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR SUPPRESSES LIPOPOLYSACCHARIDE-INDUCED OSTEOCLAST-LIKE CELL-FORMATION IN MOUSE BONE-MARROW CULTURES

Lipopolysaccharide (LPS) is a potent bone resorbing factor. We investigated the effect of LPS on osteoclast formation in three types of cultures. LPS inhibited osteoclast formation induced by 1,25-dihydroxyvitamin D-3 [1,25(OH)(2)D-3], in a dose-dependent manner, in cultures of whole bone marrow cells without dexamethasone. LPS increased the amount of granulocyte-macrophage colony stimulating factor (GM-CSF) in the culture supernatant, and anti-GM-CSF antiserum almost abolished the inhibition of osteoclast formation by LPS, thereby indicating that GM-CSF generated by treatment with LPS may be responsible for the inhibition of osteoclast formation. In cultures with dexamethasone, the amount of GM-CSF was decreased to one-third of that with 1,25(OH)(2)D-3 alone and was not changed by treatment with LPS. In this culture system, LPS enhanced osteoclast formation. In the coculture system of nonadherent bone marrow cells and a stromal cell line in the presence of 1,25(OH)(2)D-3 and dexamethasone, where no detectable GM-CSF was present in the supernatant, LPS markedly enhanced osteoclast formation, whereas exogenously added GM-CSF (100 pg/ml) almost completely inhibited osteoclast formation. LPS stimulated pit formation on dentin slices by the osteoclast-like cells formed by in vitro culture system.