The effect of tetracyclines on quantitative measures of osteoclast morphology.
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+].
Zaidi
M
M
Bone Research Unit, St. George's Hospital Medical School, London, UK.
Moonga
B S
BS
Huang
C L
CL
Towhidul Alam
A S
AS
Shankar
V S
VS
Pazianas
M
M
Eastwood
J B
JB
Datta
H K
HK
Rifkin
B R
BR
D000818:Animals; D002118:Calcium / Q000032:analysis / Q000378:metabolism / Q000502:physiology; D007091:Image Processing, Computer-Assisted; D016014:Linear Models; D008858:Microscopy, Phase-Contrast; D008911:Minocycline / Q000494:pharmacology; D010010:Osteoclasts / Q000737:chemistry / Q000166:cytology* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D018160:Receptors, Cytoplasmic and Nuclear / Q000032:analysis / Q000378:metabolism / Q000502:physiology; D013752:Tetracycline / Q000494:pharmacology*
D018160:Receptors, Cytoplasmic and Nuclear; C053450:4-des-dimethylaminotetracycline; D013752:Tetracycline; D008911:Minocycline; D002118:Calcium