| Project/Area Number |
23K16070
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 57050:Prosthodontics-related
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| Research Institution | Nagasaki University |
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Principal Investigator |
アルオマーリ ファラ 長崎大学, 医歯薬学総合研究科(歯学系), 特任研究員 (30951389)
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| Project Period (FY) |
2023-04-01 – 2024-03-31
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| Project Status |
Discontinued (Fiscal Year 2023)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2024: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2023: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | MRONJ / macrophage / bisphosphonate / polarization / denosumab |
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| Outline of Research at the Start |
Medication-related osteonecrosis of the jaw (MRONJ), which is one of adverse effects of antiresorptive agents, sometimes worsens oral health-related quality of life. However, the pathophysiology remains unclear and the treatment strategies have not been developed. The aim of this study is to determine the pathophysiology and develop treatment strategies by investigating the effects of macrophages and p65 molecule on MRONJ-like lesions.
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| Outline of Annual Research Achievements |
Medication-related osteonecrosis of the jaw (MRONJ) is a rare yet severe intractable disease with no definite treatment protocol. The aims of this study were: 1) to elucidate the different genetic and molecular pathways of macrophages involvement between BRONJ and DRONJ in murine models; 2) to clarify the connection of macrophage subtypes in the pathophysiology of MRONJ by performing multiple comprehensive analyses. An ultimate goal is to unravel the conjoined mechanisms of the immune and osseous systems to reach the basis of therapeutic strategies for MRONJ.
In this year, high-prevalence murine models of MRONJ-like lesions induced by combination administration of bisphosphonate or anti-RANKL antibody and cyclophosphamide with tooth extraction were created (BRONJ and DRONJ, respectively). Maxillae, spleen, sera, tibiae and femora were collected at euthanasia 2 weeks after tooth extraction. Micro computed tomography scan, hematoxylin & eosin staining, trichrome staining, TRAP staining, immunostaining such as blood and lymphatic vessels, CD38-positive M1 and CD163-positive M2 macrophages, and CD169-positive osteal macrophages, qPCR and ELISA were performed. Blood and lymphatic vessels were significantly reduced in BRONJ- but not DRONJ-like lesions. Polarization shifting of macrophages from M2 to M1 macrophages was significantly observed in both BRONJ- and DRONJ-like lesions. The number of CD169-positive osteal macrophages in bone marrow area was significantly changed.
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