Analysis of the mechanisms for the inflammatory bone resorption by an osteoclasts differentiation inhibitory peptide derived from mesenchymal stem cells.

2020 Fiscal Year Final Research Report

• Project/Area Number: 16K20652
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Orthodontics/Pediatric dentistry
• Research Institution: Iwate Medical University
• Principal Investigator: Kikuchi Emiko (青松恵美子) 岩手医科大学, 歯学部, 任期付助教 (50733854)
• Project Period (FY): 2016-04-01 – 2021-03-31
• Keywords: 間葉系幹細胞 / 破骨細胞 / 炎症性骨吸収

Outline of Final Research Achievements

In the present study, we have examined the mechanism for osteoclast differentiation and inflammatory bone resorption by an osteoclasts differentiation inhibitory peptide, scrapie-responsive gene 1 (SCRG1) , derived from mesenchymal stem cells (MSC). Mouse macrophage-like Raw264.7 cells as the osteoclast precursor were investigated activation of the intracellular signal transduction pathways and gene expression analysis after treatment with recombinant mouse SCRG1 (rmSCRG1) . As a result, rmSCRG1 was significantly enhanced the phosphorylation of ERK1/2. In addition, mrSCRG1 was promoted the expression of chemokine receptor, CCR7, not only reduced the expression of LPS-induced cheekiness, CCL22. Therefore, these results strongly suggested that SCRG1 secreted from MSC in the inflammatory tissues suppress the proinframmation and inflammatory bone resorption through a receptor complex, BST-1/β-integrin on the cell surface and activation of ERK1/2 of macrophages.

Free Research Field

歯科矯正学

Academic Significance and Societal Importance of the Research Achievements

本研究において破骨細胞分化抑制効果におけるSCRG1の作用点が明らかになることで、SCRG1を利用したペプチド製剤の開発や、シグナル伝達因子をターゲットにした薬剤の開発にも貢献できる。また破骨細胞分化を制御する分子メカニズム解明の一助となるだけでなく、歯周炎や慢性関節リウマチなど炎症性骨吸収を伴った疾患の治療法の確立にも寄与するものである。一方、歯科矯正治療においては圧迫側の破骨細胞分化制御機構を分子レベルで解明することができると、より効率的な矯正治療の実施へと繋がることが期待される。