The Effect of Periostin on Periodontal Wound Healing

Objectives: The objective of the study was to evaluate the effect of periostin in periodontal alveolar bone healing/repair. Recruitment of appropriate cells to the healing area, stabilization of the wound matrix, and cell proliferation are critical reparative events in this context. Periostin supports these processes at multiple levels.
Methods: An adenovirus periostin carrier system (AdCMV-POSTN) was designed and optimized to transfect primary human PDL cells. Cell toxicity, proliferation, migration and activation of the pathway AKT/mTOR were analyzed. Periostin gene therapy was subsequently used for delivery of a periostin enhancing construct into standardized periodontal defects in a murine model. Four groups were tested, a control (collagen scaffold alone), a hPDL-collagen scaffold, AdLuc/ hPDL-collagen scaffold and AdCMV-POSTN/ hPDL-collagen scaffold. Specimens were collected at 1 week, 3 weeks, 6 weeks and 8 weeks. Micro-CT volumetric analyses were performed, as well as histological and immunohistochemical studies performed, including hematoxylin and eosin, Masson’s trichrome, HLA staining (human leukocyte antigen), periostin, alcian blue and BMP-1 specific stains.
Results: AdCMV-POSTN treated group consistently resulted in increased cell proliferation and migration. These effects were maintained when the cells were seeded in a collagen vehicle. In vivo results showed no deleterious effects of periostin in the surgical area and better histological and volumetric outcomes. Significantly greater bone maturation in the periostin adenovirus group was observed at 3 weeks. Interestingly this group presented accentuated areas of clear endochondral bone formation as depicted morphologically and by Alcian Blue staining. These observations were not evident in any other group, and the endochondral features were only observed at three weeks. No evidence of cartilage was observed in subsequent time points, suggesting complete cartilage remodeling favoring the formation of mature bone at 6 and 8 weeks.
Conclusions: Periostin gene therapy application favored early bone maturation supported on early events of endochondral nature.