title: Recombinant human osteogenic protein-1 (OP-1) stimulates periodontal wound healing in class III furcation defects.
abstract: Osteogenic protein-1 (OP-1) is a member of the transforming growth factor beta superfamily and is a potent modulator of osteogenesis and bone cell differentiation. This preclinical study in dogs sought to assess the effects of OP-1 on periodontal wound healing in surgically created critical size Class III furcation defects. Eighteen male beagle dogs were subjected to the creation of bilateral mandibular 5 mm osseous defects. A split-mouth design was utilized which randomly assigned opposing quadrants to control therapy (surgery alone or collagen vehicle) or 1 of 3 ascending concentrations of OP-1 in a collagen vehicle (0.75 mg OP-1/g collagen, 2.5 mg/g, or 7.5 mg/g). Thus, 9 quadrants per test group received OP-1, 9 quadrants per control group received surgery alone, and 9 quadrants received collagen vehicle alone. Test articles were delivered by a surgeon masked to the treatment, and fluorogenic bone labels were injected at specified intervals post-treatment. Eight weeks after defect creation and OP-1 delivery, tissue blocks of the mandibulae were taken for masked histomorphometric analysis to assess parameters of periodontal regeneration (e.g., bone height, bone area, new attachment formation, and percent of defect filled with new bone). Histomorphometry revealed limited evidence of osteogenesis, cementogenesis, and new attachment formation in either vehicle or surgery-alone sites. In contrast, sites treated with all 3 concentrations of OP-1 showed pronounced stimulation of osteogenesis, regenerative cementum, and new attachment formation. Lesions treated with 7.5 mg/g of OP-1 in collagen regenerated 3.9+/-1.7 mm and 6.1+/-3.4 mm2 (mean +/-S.D.) of linear bone height and bone area, respectively. Furthermore, these differences were statistically different from both control therapies for all wound healing parameters (P < 0.0001). No significant increase in tooth root ankylosis was found among the treatment groups when compared to the surgery-alone group. We conclude that OP-1 offers promise as an attractive candidate for treating severe periodontal lesions.
authors.affiliation: Department of Periodontology, Harvard School of Dental Medicine, Boston, MA 02115-5888, USA. wgiannob@warren.med.harvard.edu
authors.forename: W V
authors.initials: WV
authors.lastname: Giannobile
authors.forename: S
authors.initials: S
authors.lastname: Ryan
authors.forename: M S
authors.initials: MS
authors.lastname: Shih
authors.forename: D L
authors.initials: DL
authors.lastname: Su
authors.forename: P L
authors.initials: PL
authors.lastname: Kaplan
authors.forename: T C
authors.initials: TC
authors.lastname: Chan
mesh_terms: D000539:Alveolar Process / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D000844:Ankylosis / Q000209:etiology; D015519:Bone Density; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000008:administration & dosage / Q000627:therapeutic use*; D003094:Collagen; D003739:Dental Cementum / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D004285:Dogs; D005452:Fluoresceins; D005456:Fluorescent Dyes; D017823:Furcation Defects / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology / Q000601:surgery; D006801:Humans; D008297:Male; D008334:Mandible / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology / Q000601:surgery; D010012:Osteogenesis; D017622:Periodontal Attachment Loss / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology / Q000601:surgery; D014677:Pharmaceutical Vehicles; D011897:Random Allocation; D011994:Recombinant Proteins; D012038:Regeneration; D016037:Single-Blind Method; D014076:Tooth Diseases / Q000209:etiology; D014092:Tooth Root / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D016212:Transforming Growth Factor beta / Q000008:administration & dosage / Q000627:therapeutic use*; D014945:Wound Healing / Q000187:drug effects
chemical_list: C525819:BMP7 protein, human; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D005452:Fluoresceins; D005456:Fluorescent Dyes; D014677:Pharmaceutical Vehicles; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D003094:Collagen