Related Experiment Video
Updated: May 8, 2026

All-optical Mechanobiology Interrogation of Yes-associated Protein in Human Cancer and Normal Cells using a Multi-functional System
Published on: December 20, 2021
Regulation of neuropeptide Y Y1 receptor expression by bone morphogenetic protein 2 in C2C12 myoblasts
Naoko Kurebayashi1, Mari Sato, Toshiaki Fujisawa
1Department of Biochemistry and Molecular Biology, Graduate School of Dental Medicine, Hokkaido University, Sapporo 060-8586, Japan; Department of Dental Anesthesiology, Graduate School of Dental Medicine, Hokkaido University, Sapporo 060-8586, Japan.
Abstract:
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 osteoblasts via an autocrine mechanism.
Insights
Bone morphogenetic protein 2 (BMP2) signaling regulates Y1 receptor expression in osteoblasts. Blocking the Y1 receptor increases markers of bone formation, suggesting an autocrine role for neuropeptide Y.
Area of Science:
- Molecular Biology
- Cell Biology
- Endocrinology
Background:
- The neuropeptide Y (NPY) system is a key neural pathway involved in various physiological processes.
- The NPY-Y1 receptor axis plays a role in bone homeostasis, as indicated by high bone mass in osteoblast-specific Y1 receptor knockout mice.
- Regulation of Y1 receptor expression during osteoblast differentiation is not well understood.
Purpose of the Study:
- To investigate the role of bone morphogenetic protein (BMP) 2 signaling in regulating Y1 receptor expression in osteoblasts.
- To explore the potential autocrine mechanism of NPY action in osteoblasts.
Main Methods:
- Utilized C2C12 and MC3T3-E1 cell lines.
- Investigated Y1 receptor mRNA expression following BMP2 treatment.
- Performed co-transfection assays with Smad1 and Smad4.
- Analyzed transcriptional activity via Y1 receptor gene promoter interaction.
- Used small interfering RNA (siRNA) to knock down Y1 receptor expression.
Main Results:
- BMP2 treatment induced Y1 receptor mRNA expression in C2C12 cells.
- Co-transfection with Smad1 and Smad4 mimicked BMP2-induced Y1 receptor expression.
- Smad1/4 enhanced transcriptional activity of the Y1 receptor gene promoter.
- siRNA-mediated knockdown of Y1 receptor in MC3T3-E1 cells increased alkaline phosphatase, osteocalcin, Runx2, and osterix expression.
Conclusions:
- BMP2 signaling is a key regulator of Y1 receptor gene expression in osteoblasts.
- NPY may act on osteoblasts via an autocrine mechanism.
- Y1 receptor signaling might negatively regulate osteoblast differentiation markers.
More Related Videos
07:53Peptides from Phage Display Library Modulate Gene Expression in Mesenchymal Cells and Potentiate Osteogenesis in Unicortical Bone Defects
Published on: December 10, 2010
11:32Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter
Published on: March 27, 2020
Related Concept Videos
Receptor Downregulation in MVBs
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR activation may...
Regulation of Nuclear Protein Sorting
Transducer Mechanism: Enzyme-Linked Receptors
Major types that are helpful drug targets include:
TGF - β Signaling Pathway
Neural Regulation
Regulation of Food Intake