Keratinocytes become terminally differentiated in a process involving programmed cell death

Oral keratinocytes originate from basal cells, differentiate during migration to the surface, and finally are shed. Apoptosis occurs at the end of differentiation, but the precise relationship between terminal differentiation and apoptosis is not clear. In the present study, Bcl-xL was expressed in the basal cell and spinous cell layers, and Bax was expressed in the spinous cell and granular cell layers. In cultured keratinocytes, Bcl-xL was expressed under conditions of 0.1 mM calcium (low Ca2+) but disappeared under conditions of 1.0 mM calcium (high Ca2+); the latter induces keratinocyte differentiation. Bax was not expressed in keratinocytes with low Ca2+ but was expressed in cells with high Ca2+. Finally keratinocytes with high Ca2+ underwent apoptosis, which was detected by the TUNEL method and by 180-bp DNA fragmentation. These results suggest that the process of terminal differentiation in gingival epithelium is a pathway to apoptosis.