title: Apoptotic and anti-apoptotic factors in early human mandible development.
abstract: 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.
authors.affiliation: Department of Anatomy, Histology and Embryology, School of Medicine, University of Split, Split, Croatia.
authors.forename: Snjezana Mardesic
authors.initials: SM
authors.lastname: Brakus
authors.forename: Danijela Kalibovic
authors.initials: DK
authors.lastname: Govorko
authors.forename: Katarina
authors.initials: K
authors.lastname: Vukojevic
authors.forename: Ivana Alujevic
authors.initials: IA
authors.lastname: Jakus
authors.forename: Dominko
authors.initials: D
authors.lastname: Carev
authors.forename: Josko
authors.initials: J
authors.lastname: Petricevic
authors.forename: Mirna
authors.initials: M
authors.lastname: Saraga-Babic
mesh_terms: D051033:Apoptosis Inducing Factor / Q000032:analysis*; D001857:Bone Matrix / Q000196:embryology; D016723:Bone Remodeling / Q000502:physiology; D002113:Calcification, Physiologic / Q000502:physiology; D002356:Cartilage / Q000196:embryology; D053148:Caspase 3 / Q000032:analysis; D002452:Cell Count; D004475:Ectoderm / Q000196:embryology; D004848:Epithelium / Q000196:embryology; D005455:Fluorescent Antibody Technique; D005865:Gestational Age; D018840:HSP70 Heat-Shock Proteins / Q000032:analysis; D006801:Humans; D020287:In Situ Nick-End Labeling; D051034:Inhibitor of Apoptosis Proteins / Q000032:analysis*; D008334:Mandible / Q000196:embryology*; D008648:Mesoderm / Q000196:embryology; D009061:Mouth Mucosa / Q000196:embryology; D010006:Osteoblasts / Q000166:cytology; D010011:Osteocytes / Q000166:cytology; D010012:Osteogenesis / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D051028:bcl-2-Associated X Protein / Q000032:analysis
chemical_list: D051033:Apoptosis Inducing Factor; D018840:HSP70 Heat-Shock Proteins; D051034:Inhibitor of Apoptosis Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D053148:Caspase 3