Elucidation the pathogenic mechanism of osteonecrosis of the jaw via inflammatory cell death 'Pyroptosis'

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K23037
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0907:Oral science and related fields
• Research Institution: Jichi Medical University
• Principal Investigator: Aizawa Emi 自治医科大学, 医学部, 臨床助教 (80877621)
• Project Period (FY): 2020-09-11 – 2022-03-31
• Keywords: 顎骨壊死 / パイロトーシス

Outline of Final Research Achievements

In recent years, several animal models have been established that induce osteonecrosis of the jaw by performing tooth extraction after administration of BP preparations to mice. However, since osteonecrosis of the jaw may occur spontaneously clinically, it is presumed that there is a mechanism that cannot be fully elucidated only by research using a jaw bone necrosis inducer model by tooth extraction. Although there have been reports that BP preparations induce apoptosis in osteoclasts, the association between osteoclasts and osteonecrosis of the jaw and pyrotosis has not been reported so far, and the causes of spontaneous osteonecrosis of the jaw are unknown. Therefore, the novelty and uniqueness of this study, which focuses on inflammation and osteonecrosis of the jaw induced by pyrotosis, is considered to be very high, and the possibility of obtaining new knowledge is also high.

Free Research Field

口腔外科学

Academic Significance and Societal Importance of the Research Achievements

近年、マウスやラットなどにBP製剤を投与後、抜歯を行うことにより顎骨壊死を誘導する動物モデルはいくつか開発されている。しかしながら、臨床的には、顎骨壊死が自然発症する場合もあることから、抜歯による顎骨壊死誘導動物モデルを用いた研究だけでは解明しきれない機序が存在することが推測される。
BP製剤が破骨細胞にアポトーシスを誘導するとの報告はあるが、破骨細胞や顎骨壊死とパイロトーシスとの関連はこれまで報告されておらず、自然発症する顎骨壊死の発症要因についても不明である。従って、パイロトーシスにより誘発される炎症と顎骨壊死に着目した本研究の学術的意義は非常に高いと思われる。