Release of mechanical tension triggers apoptosis of human fibroblasts in amodel of regressing granulation tissue

In an in vitro model of granulation tissue, early passage human diploid fib roblasts under mechanical tension showed little or no apoptosis. Release of mechanical tension triggered an apoptotic response that occurred within 3- 6 h and reached a plateau by 24 h. The percentage of apoptotic cells (simil ar to 15%) remained constant up to 7 days, and after 3 days, total cell num ber declined. Identification of mechanical unloading as a stimulus for apop tosis, without application of pharmacologic or genetic intervention, is a n ovel observation that permits us to model similar events that occur during wound healing. Studies on the mechanism regulating apoptosis under these co nditions established that the apoptotic response does not require different iation of cells into myofibroblasts but is governed by a combination of mec hanical tension and growth factors in the collagen matrix. (C) 1999 Academi c Press.