open access

https://doi.org/10.14943/doctoral.k11268

https://hdl.handle.net/2115/56295

C2C12筋芽細胞におけるNeuropeptide Y Y1受容体のBMP2による発現制御

英語

Y1 receptor

2014-03-25

Hokkaido University

24

The neuropeptide Y(NPY) system is known as one of the major neural signaling pathways. NPY, produced by peripheral tissues including osteoblasts, is known to bind to the Y1 receptor. Recently, osteoblast-specific Y1 receptor knockout mice were developed and were found to have a high bone mass phenotype, indicating a role for the NPY-Y1 receptor axis as a regulator of bone homeostasis. However, regulation of Y1 receptor expression during osteoblastic differentiation remains unexplored. In the present study, we examined the role of bone morphogenetic protein (BMP) 2 signaling in regulating Y1 receptor expression. In C2C12 cells, expression of Y1 receptor mRNA was induced by BMP2. This induction was also observed after co-transfection with Smad1 and Smad4, the intracellular signaling molecules of the BMP2 signaling pathway. In a transfection assay, Smad1/4 up-regulated transcriptional activity through interaction with the Y1 receptor gene promoter. Following transfection of MC3T3-E1 cells with siRNA for the Y1 receptor, the expression of alkaline phosphatase, osteocalcin, Runx2 and osterix were increased. These results show that BMP2 signaling regulates Y1 receptor gene expression, and raises the possibility that NPY acts in osteo blasts via an autocrine mechanism.

2014-03-25

甲第11268号

博士(歯学)

(主査) 教授 藤澤 俊明, 教授 田村 正人, 教授 鈴木 邦明

歯学研究科（口腔医学専攻）

博士論文

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