Role of MSX1 in osteo/odontogenic differentiation of human dental pulp stem cells

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K20592
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Orthodontics/Pediatric dentistry
• Research Institution: Hiroshima University
• Principal Investigator: GOTO NORIKO 広島大学, 病院(歯), 歯科診療医 (10735137)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: MSX1 / 歯髄幹細胞 / 骨分化 / SREBP2 / コレステロール合成 / アルカリフォスファターゼ / RUNX2 / siRNA

Outline of Final Research Achievements

When human dental pulp stem cells were exposed to osteogenesis-induction medium, runt-related transcription factor-2 (RUNX2), bone morphogenetic protein-2 (BMP2), alkaline phosphatase (ALPL) mRNA levels, as well as alkaline phosphatase activity, increased on days 4-12 and thereafter the matrix was calcified on day 14. However, knockdown of MSX1 with small interfering RNA abolished the induction of the osteoblast-related gene expression, alkaline phosphatase activity and calcification. Interestingly, DNA microarray and PCR analyses revealed that MSX1 knockdown induced the sterol regulatory element-binding protein 2 (SREBP2) transcriptional factor and its downstream target genes in the cholesterol-synthesis pathway. Inhibition of cholesterol synthesis enhances osteoblast differentiation of various mesenchymal cells. Thus, MSX1 may downregulate the cholesterol synthesis-related genes to ensure osteoblast differentiation of human dental pulp stem cells.

Free Research Field

小児歯科