Tetracyclines induce apoptosis in osteoclasts

Chemically modified tetracyclines (CMTs) are thought to inhibit bone resorp tion through inhibition of matrix metalloproteinases. Here we report that s ome tetracyclines also induce apoptosis in rabbit osteoclasts and inhibit d ifferentiation and activity of osteoclasts in murine osteoblast/marrow cocu ltures. Apoptosis of mature rabbit osteoclasts increased from 5.5 +/- 1.4% (mean +/- SD) in control cultures to 44.9 +/- 6.3% (p < 0.001) and 18.9 +/- 4.0% (p < 0.005) with CMT-3 and doxycycline (10 mu g/mL), respectively. CM T-2 or CMT-5 did not alter osteoclast viability even at 25 mu g/mL. In muri ne osteoblast/marrow cocultures over 11 days, CMT-3 and doxycycline (5 mu g /mL) reduced the formation of mature osteoclasts and inhibited resorption t o 21 +/- 9% (p < 0.01) and 49 +/- 4% (p < 0.01) of untreated cultures. Indu ction of osteoclast apoptosis is an additional property of tetracyclines th at may contribute to their ability to inhibit bone resorption, (Bone 27:75- 80; 2000) (C) 2000 by Elsevier Science Inc. All rights reserved.