Analysis of stem-cell aging by targeting miR-34a-SATB2 axis

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K17064
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 57030:Conservative dentistry-related
• Research Institution: Osaka University
• Principal Investigator: Ikegami Kuniko 大阪大学, 歯学部附属病院, 医員 (80779116)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: 歯周病 / 老化 / 歯根膜細胞 / miR-34a / SATB2 / ステムセルエイジング

Outline of Final Research Achievements

Periodontitis is a chronic inflammatory disease characterized by the destruction of periodontal tissue, and its prevalence increases with age. MicroRNAs (miRNAs) are stress-responsive small RNAs that have been reported to be involved in the regulation of senescence and lifespan in small animals, suggesting the involvement of cellular senescence and stem cell aging. We found that miR-34a is strongly expressed in senescent periodontal cells and targets SATB2 (a gene that promotes hard tissue formation). miR-34a-transfected cells and SATB2- knocked down cells showed decreased expression of calcification-related genes under the calcification-induced culture. This study demonstrates that regulation of SATB2 expression by miR-34a in senescent periodontal ligament cells is partly responsible for stem-cell aging, loss of stem-cellness, of the periodontal ligament cells.

Free Research Field

歯周病学

Academic Significance and Societal Importance of the Research Achievements

歯根膜は、歯周組織の修復・再生にとり重要な組織である。老化歯根膜細胞においてはmiRNA-34の発現が増加し、その標的遺伝子であるSATB2（硬組織形成を促進する遺伝子）の発現は減少していたことから、miR-34aがSATB2を調節制御していることが示唆された。miR-34aを遺伝子導入した細胞株、SATB2を欠失させた細胞株において石灰化関連遺伝子の発現は減少しており、miR-34a-SATB2経路が歯根膜細胞の複製能・分化能に影響を及ぼすことが示唆されたことより、高齢者の歯周病の予防、再生治療の有効な治療標的となる可能性が示唆された。