MKP-1 Protects from Inflammatory Bone Loss

Introduction:  The mitogen-activated protein kinase phosphatase (MKP) family plays an important function regulating the biosynthesis of pro-inflammatory cytokines by deactivating MAP kinases. MKP-1, the archetypal member of this family, is essential for the dephosphorylation of p38 MAP kinase that regulates expression of many pro-inflammatory cytokines production including IL-6, TNF-a and IL-1b.

Objectives: In this study we sought to understand the in vivo role of MKP-1 in the inflammatory bone loss models of experimental periodontitis.

Methods: 10 wild-type and 10 MKP-1 null littermates mice received A. actinomycetemcomitans Y4 strain LPS injection (20mg total) in left palatal region and PBS (vehicle control) injection in right palatal region for 30 days (3 times/week). Mice were sacrificed and micro-CT, TRAP staining, histological, and Immunohistochemistry (IHC) evaluation were utilized to measure the bone loss and extent of inflammation.

Results: By micro-CT analysis, the bone volume fraction (BVF) and linear bone loss evaluated on MKP-1 KO LPS side showed significantly greater bone loss than the MKP-1 KO control side and the wild type (p<0.001). The MKP-1 KO LPS side showed more positive TRAP cells than the MKP-1 KO control side and the wild type (p<0.033).  Similarly, IHC analysis of phospo-p38 showed increased reactivity in MKP-1 KO side than the MKP-1 KO control side and the wild type mice.

Conclusion: The MKP-1 negatively regulates the p-38 function and plays a key role in regulation of inflammatory bone loss.

These studies were supported by NIDCR 1R01DE018290-01.