Effect of Prostaglandin E2 and Lipoxin A4 on Bone Healing

Bone healing involves complex series of events which are regulated by various factors. Objectives: Aim of this study was to determine the effect of prostaglandin E2 (PGE2) and lipoxin A4 (LXA4) on bone healing of a standardized (1.00 mm) surgical defect in the rat mandible. Methods: PGE2 (controlled release pellet delivering 0.5mg PGE2/day) or LXA4 (500ngm submucosal injection) were delivered to the site of the defect. Following placement of the surgical defect,animals were sacrificed after 24hrs, 5, 10 and 20 days. Undecalcified mandibles were examined using confocal microscopy. Transverse serial sections of decalcified mandibles were stained with haematoxylin and eosin, Masson’s trichrome, for tartrate-resistant acid phosphatase, osteocalcin and osteopontin. Results: After 24 hrs the defect contained a blood clot and by day 5, immature granulation tissue was present within the defect. By day 10, increased numbers of osteocytes and osteoclasts were observed and the depth of the defect was reduced by 310microns. At day 20, the defect was occluded with unmineralized matrix, and the depth was reduced by 365microns. Following PGE2 application, defect was reduced by 600microns at day 10, contained increased numbers of osteocytes and osteoclasts, and the expression of osteopontin was upregulated. At day 20 the depth of the defect was reduced by 690microns and there was evidence of loss of adjacent alveolar bone, increased osteoclast numbers and increased expression of osteopontin and osteocalcin. In LXA4-treated tissue, unmineralized matrix formation was delayed, and the depth of the defect was reduced by only 400microns at day 10 and remained unchanged at day 20. The number of osteoclasts was reduced and the expression of osteopontin and osteocalcin was upregulated. Conclusion: PGE2 initially enhanced healing, but later appeared to induced bone resorption. LXA4 did not enhance healing and mineralized tissue formation in this model. Supported by the NHMRC and ADRF.