Osteopontin Regulates Infection-stimulated Periapical Bone Loss

Objective: Osteopontin (OPN), a secreted integrin-binding phosphoprotein, is implicated in the immune response in a number of situations. OPN functions to regulate the TH1/TH2 balance and the accumulation and function of macrophages and neutrophils. Since the development and resolution of inflammatory lesions in the periapical root area depends on macrophage and neutrophil function, we hypothesize that OPN can regulate this process.

Methods: Periapical lesions were induced in the first molars of wild-type (WT) and OPN-deficient (-/-) mice by pulp exposure and inoculation of common endodontic bacteria. At different times after infection, mice were sacrificed, and the infected root areas dissected and processed for immunohistochemistry, RNA extraction, or assessed for bone loss by micro CT.

Results: At twenty-one days after infection, OPN-/- mice had significantly greater bone loss than WT mice (p=0.0003). This bone loss was accompanied by a larger area of inflammation surrounding the site of infection, measured by analysis of H+E stained sections. There was a trend towards lower numbers of neutrophils and a higher number of macrophages in the lesion areas of the OPN-/- mice. Cytokine expression was examined by quantitative RT-PCR – the largest difference was seen in IL-1 beta expression, which was higher in WT mice than in OPN-/- animals three days after infection. Taken together, these results are consistent with a model in which OPN is expressed at the site of infection, and acts to facilitate migration of neutrophils and macrophages out of the circulation into the area of infection. In the absence of OPN, reduced neutrophil or macrophage numbers and/or function may result in reduced bacterial killing. The increased bacterial load ultimately results in an increased inflammatory response and increased bone loss.

Conclusion: These results suggest that OPN may have therapeutic value in oral infections.

Supported by NIH # DK067685 (SRR) and by DE-15888 (HS).