Apoptotic and anti-apoptotic factors in early human mandible development.

The regulators of apoptosis Bcl-2, Bax, caspase-3, p53, and Hsp70 were analyzed immunohistochemically in the developing human mandible of eight human conceptuses from weeks 5 to 10 of gestation. During this period, all proteins displayed an increased pattern of expression in the mandible ectomesenchyme and in newly formed bone, except for caspase-3, which showed decreased expression in the ectomesenchyme, but appeared first in the ossification zone at the 7th wk of development. Simultaneously, the oral epithelium showed weak (p53) to strong (hsp70) expression of all proteins investigated, while in Meckel's cartilage cells, bcl-2 was expressed weakly and hsp70 was expressed moderately. Cells on the surface of the forming bone were predominantly bax positive, and only occasionally bcl-2 positive. Only a few cells on the surface and inside the bony spicules co-expressed bax and bcl-2. Terminal deoxynucleotidyl transferase (TdT)-mediated biotin-dUTP nick-end labelling (TUNEL)-positive cells were found to be apoptotic osteoblasts. The expression of all proteins investigated changed dynamically during early mandible development and the subsequent differentiation of Meckel's cartilage and bone. While interactions between those factors might be associated with the survival of Meckel's cartilage, in the ossification zone they might participate in the control of cell numbers, mineralization, and bone remodelling. Among many other factors, precise orchestration of pro- and anti-apoptotic factors contributes to normal mandible development.