Significance of the Immunohistochemical Expression of Bone Morphogenetic Protein-4 in Bone Maturation after Maxillary Sinus Grafting in Humans.

Abstract

Bone morphogenetic proteins (BMPs) are members of the transforming growth factor-β (TGFβ) protein superfamily and are known to be involved in bone and cartilage formation. Within this family, BMP-4 is one of the most studied members. It has been shown to induce osteogenic differentiation of osteoblasts and osteoprogenitor cells in vitro, but the intimate processes in which this protein promotes and regulates osseous repair still remains unclear. To assess whether the native cellular immunohistochemical expression of BMP-4 correlates with the maturation of bone samples obtained at 6 months after maxillary sinus augmentation. Histopathological and histomorphometrical analyses were performed in all the samples, which were obtained from a total of 58 patients. Immunohistochemical expression of BMP-4 was analyzed in 30 core biopsies obtained from maxillary sinuses grafted with a combination of anorganic bovine bone and autogenous cortical bone [1:1] (AB-group), and 18 biopsies from maxillary sinuses grafted solely with a cortico-cancellous particulate allograft (M-group), all of them after a 6-month healing period. Also, 10 biopsies of native pristine bone were obtained and used as control group (C-group). Mild to moderate immunohistochemical expression of native granular BMP-4 was present in 56.8% (31.0% AB-group, 22.4% M-group, and 3.4% C-group) (p = 0.000, chi-square) of the specimens analyzed. BMP-4 expression was primarily located in the cytoplasm of osteoblasts, osteoclasts, and epithelial cells of the schneiderian membrane. Whereas significant differences were observed in the proportion of mineralized tissue and cellularity between sinuses grafted with anorganic bovine bone, allograft, or nongrafted sinuses, there were no statistically significant differences in the cellular expression of BMP-4 among groups. Our findings suggest that the native expression of BMP-4 appears to be associated with normal bone homeostasis and reparation in grafted and nongrafted maxillary sites.