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- Title
Homeobox protein MSX‐1 inhibits expression of bone morphogenetic protein 2, bone morphogenetic protein 4, and lymphoid enhancer‐binding factor 1 via Wnt/β‐catenin signaling to prevent differentiation of dental mesenchymal cells during the late bell stage
- Authors
Feng, Xiao‐Yu; Wu, Xiao‐Shan; Wang, Jin‐Song; Zhang, Chun‐Mei; Wang, Song‐Lin
- Abstract
Homeobox protein MSX‐1 (hereafter referred to as MSX‐1) is essential for early tooth‐germ development. Tooth‐germ development is arrested at bud stage in <italic>Msx1</italic> knockout mice, which prompted us to study the functions of MSX‐1 beyond this stage. Here, we investigated the roles of MSX‐1 during late bell stage. Mesenchymal cells of the mandibular first molar were isolated from mice at embryonic day (E)17.5 and cultured in vitro. We determined the expression levels of <italic>β</italic>‐catenin, bone morphogenetic protein 2 (<italic>Bmp2</italic>), <italic>Bmp4</italic>, and lymphoid enhancer‐binding factor 1 (<italic>Lef1</italic>) after knockdown or overexpression of <italic>Msx1</italic>. Our findings suggest that knockdown of <italic>Msx1</italic> promoted expression of <italic>Bmp2</italic>,<italic> Bmp4</italic>, and <italic>Lef1</italic>, resulting in elevated differentiation of odontoblasts, which was rescued by blocking the expression of these genes. In contrast, overexpression of <italic>Msx1</italic> decreased the expression of <italic>Bmp2</italic>,<italic> Bmp4</italic>, and <italic>Lef1</italic>, leading to a reduction in odontoblast differentiation. The regulation of <italic>Bmp2</italic>,<italic> Bmp4</italic>, and <italic>Lef1</italic> by <italic>Msx1</italic> was mediated by the Wnt/<italic>β</italic>‐catenin signaling pathway. Additionally, knockdown of <italic>Msx1</italic> impaired cell proliferation and slowed S‐phase progression, while overexpression of <italic>Msx1</italic> also impaired cell proliferation and prolonged G1‐phase progression. We therefore conclude that MSX‐1 maintains cell proliferation by regulating transition of cells from G1‐phase to S‐phase and prevents odontoblast differentiation by inhibiting expression of <italic>Bmp2</italic>,<italic> Bmp4</italic>, and <italic>Lef1</italic> at the late bell stage via the Wnt/<italic>β</italic>‐catenin signaling pathway.
- Subjects
ANIMAL experimentation; BONE morphogenetic proteins; CELLULAR signal transduction; GENE expression; MICE; STEM cells; TRANSCRIPTION factors; DNA-binding proteins; WNT proteins; FETAL development
- Publication
European Journal of Oral Sciences, 2018, Vol 126, Issue 1, p1
- ISSN
0909-8836
- Publication type
Article
- DOI
10.1111/eos.12390