EXPRESSION ON OUTER MEMBRANES OF MANNOSE RESIDUES, WHICH ARE INVOLVEDIN OSTEOCLAST FORMATION VIA CELLULAR FUSION EVENTS

Osteoclast, the bone-resorbing cell, is formed from hematopoietic prec ursors via cell cell fusion. To evaluate the possibility that under ce rtain specific conditions mannose residues may be expressed on the mam malian cell surface, we examined the action of pradimicin derivatives, which bind specific sugars such as the mannose residue, on the format ion of osteoclast induced in the coculture of mouse spleen cells with mouse stromal cells, a process in which cell cell fusion is involved. Osteoclast formation was inhibited by treatment of this coculture syst em with pradimicin at the later stage (day 4-7), and this inhibition w as specifically abrogated by mannose-rich yeast mannan. During the 8-d ay cocultivation, osteoclast formation was blocked by the pradimicin o n days 6 and 7, when mononuclear preosteoclasts fused into multinuclea ted osteoclasts. With an interactive laser cytometer ACAS570, fluoresc ein isothiocyanate-labeled pradimicin was observed to bind osteoclast progenitors at the fusion stage and to have no binding affinity for os teoclast progenitors at the early stage (day 0-3) or for osteoclasts, which were formed after performing fusion between mononuclear preosteo clasts. These results suggest that mannose residues were expressed on outer membranes of monocytes under pathophysiological conditions and t hat they were involved in the osteoclast formation via cellular membra ne fusion events.