The effect of tetracyclines on quantitative measures of osteoclast morphology.
Zaidi M., Moonga BS., Huang CL., Towhidul Alam AS., Shankar VS., Pazianas M., Eastwood JB., Datta HK., Rifkin BR.
We report the effects of the tetracycline analogues 4-dedimethylaminotetracycline (CMT-1) and minocycline on osteoclast spreading and motility. Both agents influenced the morphometric descriptor of cell spread area, rho, producing cellular retraction or an R effect (half-times: 30 and 44 minutes for CMT-1 and minocycline, respectively). At the concentrations employed, the tetracycline-induced R effects were significantly slower than, but were qualitatively similar to, those resulting from Ca2+ "receptor" activation through the application of 15 mM-[Ca2+] (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 same tetracycline concentrations did not influence osteoclast margin ruffling activity as described by mu, a motility descriptor known to be influenced by elevations of cellular cyclic AMP. Thus, the tetracyclines exert morphometric effects comparable to changes selectively activated by occupancy of the osteoclast Ca2+ "receptor" which may act through an increase in cytosolic [Ca2+].