Sexual dimorphism in periapical inflammation and bone loss from mitogen-activated protein kinase phosphatase-1 deficient mice

Introduction: Mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1) has been shown to be a key negative regulator of the MAPK pathways of the innate immune system. The impact of MKP-1 in an endodontic model has yet to be studied. Thus, the purpose of this study was to determine the role of MKP-1 in a bacterial-driven model of pathologic endodontic bone loss. Methods: Pulps were exposed in both lower first molars of 10-week-old mkp-1^+/+ and mkp-1^-/- mice and left open to the oral environment for either 3 or 8 weeks. At death, mandibles were harvested and scanned by micro-computed tomography (μCT) to determine periapical bone loss. Histopathologic scoring was then performed on the samples to determine the amount of inflammatory infiltrate within the periapical microenvironment. Results: Significant bone loss and inflammatory infiltrate were found in all experimental groups when compared with control. No statistical difference was found between mkp-1 ^+/+ and mkp-1^-/- at either time point with respect to bone loss or inflammatory infiltrate. At 8 weeks, male mkp-1^-/- mice were found to have significantly more bone loss and inflammatory infiltrate when compared with female mkp-1^-/- mice. There was also a significant correlation between an increase in bone loss and increase in inflammatory infiltrate. Conclusions: A sexual dimorphism exists in the periapical inflammatory process, where male mkp-1^-/- mice have more inflammation than female mkp-1^-/- mice. The increase in inflammatory infiltrate correlates to more bone loss in the male mice.