The transduction of mechanical force into biochemical events in bone cells may involve activation of phospholipase A2

Abstract

Mechanical forces applied to cultured bone cells induce the production of cAMP via stimulation of the formation of prostaglandin E₂ (PGE₂) and its release into the medium, resulting in stimulation of adenylate cyclase. In this paper we show that either the antibiotic gentamycin (100 μg/ml) or antiphospholipid antibodies (0.1%) which bind to membrane phospholipids abolish cAMP formation induced by mechanical forces; exogenously added arachidonic acid or PGE₂ stimulates cAMP formation, even in the presence of these agents. Addition of exogenous phospholipase A₂ (but not phospholipase C) causes an increase in the formation of cAMP in bone cells, a response that is also inhibited by gentamycin or antiphospholipase antibodies. These observations suggest that mechanical forces exert their effect on bone cells via the following chain of events: (1) activation of phospholipase A₂, (2) release of arachidonic acid, (3) increased PGE synthesis, (4) augmented cAMP production.