Evidence for apoptosis induction in myofibroblasts during palatal mucoperiosteal repair

Apoptosis is thought to be a requisite event for maintaining kinetic homeostasis within continually renewing tissues such as the oral mucosa and skin. However, no systematic study of the apoptotic process in fibroblasts in the oral mucosa following injury has been performed. In this study, we have assessed the expression of transforming growth factor-beta1 (TGF-beta1) and basic fibroblast growth factor (bFGF), which are among the most important modulators of wound repair, during wound healing following mucoperiosteal injury in the rat palate. In addition, we have investigated fibroblast differentiation and apoptosis by immunohistochemical analysis for alpha-smooth-muscle (alpha-SM) actin or DNA strand breaks, respectively, to clarify the mechanisms of the wound healing process. TGF-beta1-positive cells were noted in the subepithelium from Day 2 to Day 14 after injury, by which time the wounds were completely reepithelialized. Strong expression of bFGF was observed, mainly in macrophages and monocytes at the injured site, from Day 10 to Day 14 after injury. TGF-beta1 and bFGF-immunostaining was significantly lower during the later phase of wound healing. In addition, the number of myofibroblasts expressing alpha-SM actin increased (peak at Day 14), and thereafter gradually decreased. In parallel, the apoptosis in myofibroblasts was prominent on Day 14. These results suggest that TGF-beta1 and bFGF may be potential stimulators of apoptosis in myofibroblasts after re-epithelialization in the palatal wound healing process. The regulation of apoptotic phenomena during wound healing may be important in scar establishment and development of pathological scarring.