title: Recombinant Human Bone Morphogenetic Protein 9 (rhBMP9) Induced Osteoblastic Behavior on a Collagen Membrane Compared With rhBMP2.
abstract: Bone morphogenetic protein 9 (BMP9) has previously been characterized as one of the most osteogenic growth factors of the BMP family. To the best of the authors' knowledge, previous experiments have only used adenovirus transfection (gene therapy). With the recent development of recombinant human BMP9 (rhBMP9), the present study investigates the osteopromotive potential of BMP9 versus rhBMP2 when loaded onto collagen membranes.
  
  
  
  ST2 stromal bone marrow cells were seeded onto: 1) control; 2) low-dose rhBMP2 (10 ng/mL); 3) high-dose rhBMP2 (100 ng/mL); 4) low-dose rhBMP9 (10 ng/mL); and 5) high-dose rhBMP9 (100 ng/mL) porcine collagen membranes. The following parameters were compared among groups: 1) cell adhesion (at 8 hours); 2) cell proliferation (at 1, 3, and 5 days); 3) real-time polymerase chain reaction for genes encoding runt-related transcription factor 2; 4) alkaline phosphatase (ALP); 5) bone sialoprotein ([BSP] at 3 and 14 days); and 6) alizarin red staining (at 14 days).
  
  
  
  rhBMP2 and rhBMP9 demonstrated little effect on cell attachment and proliferation; however, pronounced increases were observed in osteoblast differentiation. All groups significantly induced ALP messenger RNA (mRNA) levels at 3 days and BSP levels at 14 days; however, high-dose rhBMP9 showed significantly higher values compared with all other groups for ALP levels (five-fold increase at 3 days and two-fold increase at 14 days). Alizarin red staining further revealed both concentrations of rhBMP9 induced up to three-fold more staining compared with rhBMP2.
  
  
  
  Results indicate that the combination of collagen membranes with rhBMP9 induced significantly higher ALP mRNA expression and alizarin red staining compared with rhBMP2. These findings suggest that rhBMP9 may be a suitable growth factor for future regenerative procedures in bone biology.
authors.affiliation: Department of Operative, Preventive and Pediatric Dentistry, University of Bern, Bern, Switzerland.|Department of Oral Surgery, Institute of Biomedical Sciences, Tokushima University, Tokushima, Japan.
authors.forename: Masako
authors.initials: M
authors.lastname: Fujioka-Kobayashi
authors.affiliation: Department of Operative, Preventive and Pediatric Dentistry, University of Bern, Bern, Switzerland.|Advanced Research Center, School of Life Dentistry at Niigata, The Nippon Dental University, Niigata, Japan.
authors.forename: Kosaku
authors.initials: K
authors.lastname: Sawada
authors.affiliation: Department of Operative, Preventive and Pediatric Dentistry, University of Bern, Bern, Switzerland.
authors.forename: Eizaburo
authors.initials: E
authors.lastname: Kobayashi
authors.affiliation: Department of Operative, Preventive and Pediatric Dentistry, University of Bern, Bern, Switzerland.
authors.forename: Benoit
authors.initials: B
authors.lastname: Schaller
authors.affiliation: Department of Oral Implantology, Wuhan University, Wuhan, China.
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Periodontology, School of Dental Medicine, University of Bern.|Department of Periodontology, College of Dental Medicine, Nova Southeastern University, Fort Lauderdale, FL.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Miron
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism* / Q000502:physiology*; D000818:Animals; D055396:Bone Morphogenetic Protein 2; D002454:Cell Differentiation; D002478:Cells, Cultured; D003094:Collagen / Q000502:physiology*; D055427:Growth Differentiation Factor 2; D055412:Growth Differentiation Factors; D006801:Humans; D010006:Osteoblasts / Q000502:physiology*; D010012:Osteogenesis; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D055396:Bone Morphogenetic Protein 2; C525887:GDF2 protein, human; D055427:Growth Differentiation Factor 2; D055412:Growth Differentiation Factors; D003094:Collagen; D000469:Alkaline Phosphatase
keywords: Bone morphogenetic protein 2; bone regeneration; osteogenesis; recombinant proteins