Bone morphogenetic protein-2 stimulates cell recruitment and cementogenesis during early wound healing

J Clin Periodontol. 2001 May;28(5):465-75. doi: 10.1034/j.1600-051x.2001.028005465.x.

Abstract

Background: The unique action of bone morphogenetic proteins (BMPs) on mineralised tissue formation indicates that BMPs are good candidates for use in stimulating periodontal regeneration. Relatively little is known about the mechanisms of actions of BMPs during periodontal regeneration, although recent evidence from our laboratory suggests that the effects of BMPs may be profoundly influenced by various factors including root surface conditioning, delivery systems and masticatory forces.

Aim: The aim of this study was to investigate the effect of rhBMP-2 on cell recruitment during periodontal regeneration using a pulse-chase technique where cells are labelled with a thymidine analogue (BrdU) (pulse) and the migration of their progeny is followed (chase) during early wound healing. The relationship between the rhBMP-2 influence on cell recruitment from the periodontal ligament (PDL) and its ability to stimulate cementogenesis was also evaluated.

Method: The buccal aspect of the distal root of the first molar was denuded of its PDL, cementum and superficial dentine through a bony window created in the mandible of 64 Wistar rats under general anaesthesia. Test animals were treated with 10 microL of 500 microg/ml rhBMP-2 in a collagen membrane sponge (n=32) and control defects received 10 microl of saline in a collagen sponge (n=32). All animals received an intraperitoneal single pulse injection of 40 mg/kg BrdU label 2 days postoperatively. Groups of test and control animals (n=8) were killed 2 hours later on day 2 and at 4, 7 and 10 days postoperatively. Mandibles were processed for histological examination.

Results: The results show that rhBMP-2 had a profound effect on proliferation and migration of cells in the adjacent and deeper aspects of the PDL at 7 and 10 days post periodontal wounding (p<0.05). Significantly greater new cementum formation occurred in the test group at 10 days (p=0.03).

Conclusion: This study shows that following periodontal wounding rhBMP-2 stimulates cell recruitment by increasing proliferation and migration of cells from the adjacent unwounded PDL into the wounded area, thus promoting periodontal regeneration by increasing new cementum formation.

MeSH terms

  • Alveolar Bone Loss / pathology
  • Alveolar Bone Loss / physiopathology
  • Animals
  • Antibodies, Monoclonal
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Proteins / therapeutic use*
  • Bromodeoxyuridine
  • Cell Division / drug effects
  • Cell Movement
  • Collagen
  • Coloring Agents
  • Dental Cementum / drug effects*
  • Dental Cementum / pathology
  • Dental Cementum / physiopathology
  • Gelatin Sponge, Absorbable
  • Indicators and Reagents
  • Membranes, Artificial
  • Molar
  • Osteogenesis / drug effects
  • Periodontal Diseases / pathology
  • Periodontal Diseases / physiopathology
  • Periodontal Ligament / drug effects
  • Periodontal Ligament / pathology
  • Periodontal Ligament / physiopathology
  • Rats
  • Rats, Wistar
  • Recombinant Proteins
  • Regeneration / drug effects
  • Statistics as Topic
  • Transforming Growth Factor beta / therapeutic use*
  • Wound Healing / drug effects

Substances

  • Antibodies, Monoclonal
  • Bmp2 protein, rat
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Proteins
  • Coloring Agents
  • Indicators and Reagents
  • Membranes, Artificial
  • Recombinant Proteins
  • Transforming Growth Factor beta
  • Collagen
  • Bromodeoxyuridine