Clarification of the mechanism of bone degradation by methylglyoxal and development of methods to prevent it

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K09528
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 57010:Oral biological science-related
• Research Institution: Showa University
• Principal Investigator: Yoshimura Kentaro 昭和大学, 歯学部, 講師 (10585699)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 最終糖化産物 / 骨 / メチルグリオキサール / 活性イオウ分子種

Outline of Final Research Achievements

Methylglyoxal (MG), a by-product of glycolysis, is one of the precursors of advanced glycation end-products. We had reported that MG degrades physicochemical properties of mineralized nodules produced by osteoblasts through glycation of bridges between collagen molecules. Since MG is a nucleophilic compound, we studied the effects of reactive sulfur species having strong electrophilic properties on the degradation of mineralized nodules by MG. Suppression of the expression of RSS-producing enzyme in osteoblasts reduced their mineralization. Also, NaHS, an RSS donor, improved the osteoblastic mineralization in the presence of MG. These results suggest that RSS can prevent degradation of the bone matrix by MG.

Free Research Field

生化学

Academic Significance and Societal Importance of the Research Achievements

骨の強度は骨密度と骨質に依存する。種々の要因で、骨密度あるいは骨質が低下し、骨粗鬆症を引き起こす。2型糖尿病でも骨が脆弱になり骨折リスクが高まるが、この場合は、骨密度の低下に比較し、骨質の劣化が著しい。我々は、骨質劣化の原因の一つとしてMGによる骨基質タンパク質の糖化変性を見出した。本研究は、RSSがMGの反応性を低下させることで、２型糖尿病に伴う骨粗鬆症を予防できる可能性を示すもので、今後の治療薬開発の基礎となるものである。