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Sexual dimorphism in periapical inflammation and bone loss from mitogen-activated protein kinase phosphatase-1
Justin McAbee1, Qiyan Li, Hong Yu
1Department of Oral Rehabilitation, Division of Endodontics, Medical University of South Carolina, 173 Ashley Ave., Charleston, SC 29425, USA.
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.
Insights
Mitogen-activated protein kinase phosphatase-1 (MKP-1) does not affect endodontic bone loss. However, male mice lacking MKP-1 showed increased inflammation and bone loss compared to females.
Area of Science:
- Immunology
- Endodontics
- Oral Biology
Background:
- Mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1) is a critical negative regulator of MAPK pathways in innate immunity.
- The role of MKP-1 in endodontic pathology has not been previously investigated.
Purpose of the Study:
- To investigate the function of MKP-1 in a mouse model of bacterial-induced pathologic endodontic bone loss.
Main Methods:
- Dental pulp exposure in mkp-1(+/+) and mkp-1(-/-) mice.
- Micro-computed tomography (μCT) for periapical bone loss assessment.
- Histopathologic scoring for inflammatory infiltrate quantification.
Main Results:
- All experimental groups exhibited significant bone loss and inflammation compared to controls.
- No significant difference in bone loss or inflammation was observed between mkp-1(+/+) and mkp-1(-/-) mice.
- Male mkp-1(-/-) mice showed significantly greater bone loss and inflammation than female mkp-1(-/-) mice at 8 weeks.
- A positive correlation was found between inflammatory infiltrate and bone loss.
Conclusions:
- Sexual dimorphism influences the periapical inflammatory response, with males exhibiting heightened inflammation.
- Increased inflammation in male mkp-1(-/-) mice correlates with exacerbated bone loss.
