5-LIPOXYGENASE METABOLITES OF ARACHIDONIC-ACID STIMULATE ISOLATED OSTEOCLASTS TO RESORB CALCIFIED MATRICES

Bone resorption requires cooperation between osteoclasts and mononucle ar accessory cells by mechanisms which have not been elucidated. Since multinucleated cells in giant cell tumors of bone have many phenotypi c and functional characteristics of normal osteoclasts, we have examin ed the interaction between the bone-resorbing multinucleated cells and the distinct mono-nuclear stromal cells from these tumors. We have fo und that these mononuclear cells produce an activity which stimulates both giant cells from giant cell tumors and rodent osteoclasts to reso rb bone in vitro. We have identified the activity and found that it re presents several products of the 5-lipoxygenase pathway of arachidonic acid metabolism, namely 5-hydroxyeicosatetraenoic acid and the leukot rienes. These data indicate that 5-lipoxygenase metabolites stimulate isolated osteoclasts to resorb bone in vitro and may represent a mecha nism by which mononuclear stromal cells in human giant cell tumors com municate with the giant cells. In addition, these results may explain a possible mechanism for communication between accessory cells and ost eoclasts involved in normal bone resorption.