title: Significance of the Immunohistochemical Expression of Bone Morphogenetic Protein-4 in Bone Maturation after Maxillary Sinus Grafting in Humans.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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).
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Oral Surgery and Implant Dentistry Department, School of Dentistry, University of Granada, Granada, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Torrecillas-Martínez
authors.affiliation: Oral Surgery and Implant Dentistry Department, School of Dentistry, University of Granada, Granada, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Galindo-Moreno
authors.affiliation: Department of Periodontics, College of Dentistry, University of Iowa, Iowa City, IA, USA.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Ávila-Ortiz
authors.affiliation: Oral Surgery and Implant Dentistry Department, School of Dentistry, University of Granada, Granada, Spain.
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Ortega-Oller
authors.affiliation: Department of Periodontics and Oral Medicine School of Dentistry, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Alberto
authors.initials: A
authors.lastname: Monje
authors.affiliation: Orthopedic Surgery Department, San Cecilio University Hospital of Granada, Granada, Spain.
authors.forename: Pedro
authors.initials: P
authors.lastname: Hernández-Cortés
authors.affiliation: Department of Pathology and Biopathology and Regenerative Medicine Institute (IBIMER), School of Medicine, University of Granada, Granada, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Aguilar
authors.affiliation: Department of Pathology and Biopathology and Regenerative Medicine Institute (IBIMER), School of Medicine, University of Granada, Granada, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: O'Valle
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001706:Biopsy; D055415:Bone Morphogenetic Protein 4 / Q000378:metabolism*; D016723:Bone Remodeling / Q000502:physiology*; D016025:Bone Transplantation; D002417:Cattle; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008443:Maxillary Sinus / Q000166:cytology / Q000378:metabolism* / Q000601:surgery; D008875:Middle Aged; D010784:Photomicrography
chemical_list: D055415:Bone Morphogenetic Protein 4
keywords: biomaterials; bone grafting; bone morphogenetic protein 4; immunohistochemistry; maxillary sinus