THE EFFECT OF TETRACYCLINES ON QUANTITATIVE MEASURES OF OSTEOCLAST MORPHOLOGY

We report the effects of the tetracycline analogues 4-dedimethylaminot etracycline (CMT-1) and minocycline on osteoclast spreading and motili ty. Both agents influenced the morphometric descriptor of cell spread area, rho, producting cellular retraction or an R effect (half-times: 30 and 44 minutes for CMT-1 and minocycline, respectively). At the con centrations employed, the tetracycline-induced R effects were signific antly slower than, but were qualitatively similar to, those resulting from Ca2+ ''receptor'' activation through the application of 15 mM-[Ca 2+] (slopes: -1.25, -0.18, and -4.40/minute for 10 mg/l-[CMT-1], 10 mg /l-[minocycline] and 15 mM-[Ca2+], respectively). In contrast, the sam e tetracycline concentrations did not influence osteoclast margin ruff ling activity as described by mu, a motility descriptor known to be in fluenced by elevations of cellular cyclic AMP. Thus, the tetracyclines exert morphometric effects comparable to changes selectively activate d by occupancy of the osteoclast Ca2+ ''receptor'' which may act throu gh an increase in cytosolic [Ca2+].