Analysis of bone remodeling using iPS cells derived from the patients with phagocyte signal transduction defects

2014 Fiscal Year Final Research Report

• Project/Area Number: 25870468
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics; Immunology
• Research Institution: Hiroshima University
• Principal Investigator: TSUMURA Miyuki 広島大学, 医歯薬保健学研究院(医), 研究員 (80646274)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: 食細胞異常 / 骨髄炎 / 破骨細胞 / IFN-γ / STAT1 / IFN-γR1

Outline of Final Research Achievements

The loss-of-function formed IFN-γR1 and STAT1 deficiency presents mendelian susceptibility to mycobacterial diseases (MSMD). Osteomyelitis is a bone infection by bacteria and other microorganism, and is one of clinical features presented in more than 80% of patients with MSMD. Osteoclasts, bone-resorbing multinuclear cells, are derived from myeloid/ monocyte lineage. IFN-γ is known to strongly suppress osteoclast formation in mice. However, the mechanism and the function of IFN-γ still remains unclear. In this study, we analyzed the formation of osteoclasts and the function of osteoclast using the mononuclear phagocytes of IFN-γR1 and STAT1 deficient patients. Our results strongly show the augmented osteoclast formation and their function in patients with MSMD through the deficiency to IFN-γ-STAT1 signal. The IFN-γ-STAT1 signal transduction system in mononuclear phagocytes may play an important role in the presentation of multiple bone lesions in MSMD patients.

Free Research Field

免疫不全