2018 Fiscal Year Final Research Report
Molecular mechanisms of bone-specific immunopathology during malaria
| Project/Area Number |
16H05181
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Parasitology (including sanitary zoology)
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| Research Institution | Osaka University |
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Principal Investigator |
Cevayir Coban 大阪大学, 免疫学フロンティア研究センター, 教授 (00397712)
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| Research Collaborator |
ISHII Ken
AKIRA Shizuo
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Keywords | Bone loss / osteoclast / osteoblast / malaria / Vitamin D / RANKL / MyD88 / Plasmodium |
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| Outline of Final Research Achievements |
Malaria has deadly complications; however, the long term pathological consequences of chronic malaria infection are poorly understood. We suspected that there is an association between growth retardation and malaria infection. Therefore, we investigated possible negative impact of malaria infection on bone remodeling and growth. Using mouse models mimicking chronic and self-clearing Plasmodium infection we showed that infection causes significant and long term bone loss in adult mice and growth retardation in young mice. Bone remodeling is completely suppressed during the acute phase of infection, but is highly activated immediately after the clearance of parasites, with increased osteoclastic activity skewing the balance toward bone resorption. Osteoclasts are activated by the key osteclastogenic cytokine RANKL, which was upregulated in osteoblasts through MyD88-dependent inflammation, triggered by the accumulation and long term persistence of parasite products in the bone marrow.
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| Free Research Field |
Immunoparasitology
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| Academic Significance and Societal Importance of the Research Achievements |
Our results highlight the risk of bone loss in malaria-infected patients. Bone loss is sustained even after recovery from malaria.Therapies promoting bone health like Vitamin D treatment coupled with anti-malarial treatment may help to improve bone health in malaria-infected individuals.
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