Abstract
The mitogen-activated protein (MAP) kinase phosphatase (MKP) family plays an important function in regulating the pro-inflammatory cytokines by deactivating MAP kinases. MKP-1 is essential for the dephosphorylation of p38 MAP kinase that regulates expression of IL-6, TNF-alpha, and IL-1 beta. We hypothesized that MKP-1 regulates inflammatory bone loss in experimental periodontitis. Wild-type and Mkp-1(-/-) mice received A. actinomycetemcomitans LPS injection in the palatal region or PBS control 3 times/wk for 30 days. Mice were killed, and maxillae were assessed by microcomputed tomography, histological analysis, and TRAP staining for measurement of bone loss, extent of inflammation, and degree of osteoclastogenesis. Results indicated that, in LPS-injected Mkp-1(-/-) mice, significantly greater bone loss occurred with more inflammatory infiltrate and a significant increase in osteoclastogenesis compared with Mkp-1(-/-) control sites or either wild-type group. Analysis of these data indicates that MKP-1 plays a key role in the regulation of inflammatory bone loss.
Publication types
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Comparative Study
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Research Support, N.I.H., Extramural
MeSH terms
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Acid Phosphatase / analysis
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Aggregatibacter actinomycetemcomitans / physiology
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Alveolar Bone Loss / enzymology*
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Alveolar Bone Loss / pathology
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Alveolar Bone Loss / prevention & control
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Animals
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Biomarkers / analysis
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Cell Count
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Cell Line
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Cone-Beam Computed Tomography
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Dual Specificity Phosphatase 1 / immunology
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Dual Specificity Phosphatase 1 / physiology*
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Imaging, Three-Dimensional
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Immunity, Innate / immunology
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Interleukin-6 / analysis
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Interleukin-6 / metabolism
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Isoenzymes / analysis
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Leukocytes / pathology
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Lipopolysaccharides / pharmacology
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Maxillary Diseases / enzymology
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Maxillary Diseases / pathology
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Maxillary Diseases / prevention & control
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Mice
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Mice, Knockout
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Osteoclasts / pathology
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Palate
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Periodontitis / enzymology
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Periodontitis / microbiology
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Phosphorylation
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Tartrate-Resistant Acid Phosphatase
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Time Factors
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X-Ray Microtomography
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p38 Mitogen-Activated Protein Kinases / analysis
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p38 Mitogen-Activated Protein Kinases / metabolism
Substances
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Biomarkers
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Interleukin-6
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Isoenzymes
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Lipopolysaccharides
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p38 Mitogen-Activated Protein Kinases
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Acid Phosphatase
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Acp5 protein, mouse
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Tartrate-Resistant Acid Phosphatase
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Dual Specificity Phosphatase 1