2023 Fiscal Year Final Research Report

Elucidation of the mechanism of ectopic calcification by high-resolution mass spectrometry

Research Project

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Project/Area Number	21K09873
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 57030:Conservative dentistry-related
Research Institution	Osaka University
Principal Investigator	Shimizu Masato 大阪大学, 歯学部附属病院, 医員 (70380277)
Co-Investigator(Kenkyū-buntansha)	上垣浩一近畿大学, 農学部, 教授 (00356544) 野崎剛徳大阪大学, 歯学部附属病院, 准教授 (30263304) 三浦治郎大阪大学, 歯学部附属病院, 助教 (70437383)
Project Period (FY)	2021-04-01 – 2024-03-31
Keywords	糖化最終産物（AGEs） / 歯髄内結石 / 架橋型AGEsペントシジン / AGEs阻害薬アラゲブリウム / RAGE阻害薬FPS-ZM1 / 蛍光分析 / 質量顕微鏡 / 免疫染色
Outline of Final Research Achievements	The carbonyl group of a reducing sugar binds to an amino group of proteins and is chemically modified by a series of reactions, such as Amadori rearrangement and oxidation. This series of reaction is named Maillard reaction, which occurs under physiological conditions is irreversible. The final products of this reaction are called advanced glycation end products (AGEs). Alagebrium is a chemical compound of potent anti-AGEs. Clinical reports on positive effects of administration of alagebrium for conditions such as hypertension due to arteriosclerosis exist in the literature. In vitro studies have reported that alagebrium digests AGE crosslinkers; this was demonstrated by a difference in the pattern of peptide mapping of collagen molecules with CNBr digestion. However, direct interaction between AGEs and alagebrium has not been reported. Thus, the present study was undertaken to analyze the direct or indirect interaction of AGEs with alagebrium, using western blot and HPLC analyses.
Free Research Field	歯科保存分野
Academic Significance and Societal Importance of the Research Achievements	生体内のタンパク質の糖化によって生成した糖化最終産物（AGEs)のうち、特にタンパク質分子間を架橋する架橋型AGEsはタンパク質の代謝を阻害することで蓄積し、動脈硬化や骨粗鬆症など多くの疾病に関わっていると考えられている。歯科においては歯髄内部など異所性の石灰化を引き起こすとこが知られていたが、本研究ではAGEs阻害薬やAGEs受容体（RAGE)阻害薬を用い、解析にあたっては免疫染色やHPLC、質量顕微鏡など解析方法を駆使することで異所性石灰化のカスケードの解析を行い、タンパク質の糖化→架橋型AGEs→石灰化流れを明らかにした。糖化が原因と考えられている他の疾病への応用も可能だと考えられる。