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.

Noggin Gene Delivery Inhibits Cementoblast-Induced Mineralization

“…BMP-2 was shown to induce dental follicle cell differentiation into cementoblasts/osteoblasts in vitro [8]. BMP-2 and BMP-7 promote osteogenesis and cementogenesis in critical size periodontal defects in dogs [9,22]. Although BMP's effects on mesenchymal cell differentiation into hard tissue-forming cells (e.g., osteoblasts, cementoblasts, and odontoblasts) have been studied widely, the impact of BMPs and their antagonists on mature cementoblasts is not completely understood.…”

“…BMP-2 triggers the differentiation of dental follicle cells into cementoblasts or osteoblasts in vitro [8]. Moreover, BMPspotently stimulate alveolar bone regeneration around teeth [9], as well as initiate cementogenesis in periodontal wounds [10,11]. Therefore, BMP signaling appears to be critical in regulating periodontal tissue formation in pre-and postnatal life.…”

Bone morphogenetic proteins in human bone regeneration

“…However, reports of clinical studies have not yet been published. In dental research, BMPs have been used to stimulate periodontal wound healing in dogs, with good result (175,176); again, clinical studies are, as yet, lacking. These animal studies still indicate that BMPs have possibilities for clinical use other than bone repair alone.…”

Epithelial Cell Rests of Malassez Modulate Cell Proliferation, Differentiation and Apoptosis via Gap Junctional Communication under Mechanical Stretching in vitro

“…In addition, BMP2 potently stimulates alveolar bone regeneration around teeth, as well as cementogenesis in periodontal wounds 9) . Therefore, BMP signaling appears to be critical in regulating periodontal tissue formation in pre-and post-natal life.…”