Title: THE ROLE OF αSMA PERIVASCULAR CELLS DURING REPARATIVE DENTINOGENESIS
Abstract: OBJECTIVES: The aim of this study was to examine the contribution of perivascular
cells to odontoblasts during the development, growth, and repair of dentin and examine
the effects of early and limited exposure of perivascular cells to fibroblast growth factor
2 (FGF2) in vivo using mouse molars as a model. MATERIAL AND METHODS: We
used an inducible, Cre-loxP in vivo fate-mapping approach to examine the contributions
of the descendants of cells expressing the αSMA-CreERT2 transgene to the odontoblast
lineage. RESULTS: In vivo lineage-tracing experiments showed the contribution of
αSMA-tdTomato+ cells to a small number of newly formed odontoblasts during primary
dentinogenesis. Experiments revealed that mild injury to dentin first led to activation of
aSMA-tdTomato+ cells in the entire pulp chamber. After their activation aSMAtdTomato+
cells migrated towards the site of injury, gave rise to pulp cells and a few
odontoblasts that became integrated into the existing odontoblast layer expressing Col2.3-
GFP and Dspp. Using an experimental pulp exposure model in molars to induce
reparative dentinogenesis, we demonstrate the contribution of αSMA-tdTomato+ cells to
cells secreting reparative dentin. Our results demonstrate that αSMA-tdTomato+ cells
differentiated into Col2.3-GFP+ cells composed of both Dspp+ odontoblasts and Bsp+
osteoblasts. Early delivery of exogenous FGF2 to exposed pulp led to proliferative
expansion of αSMA-tdTomato+ cells and their accelerated differentiation into
odontoblasts. Results showed that the calcified bridge/reparative dentin in FGF2-treated
pulps were lined with an increased number of Dspp+ odontoblasts and devoid of BSP+
osteoblasts. CONCLUSION: Our findings identify a population of mesenchymal
progenitor cells capable of giving rise to a second generation of odontoblasts during
reparative dentinogenesis. The increased number of odontoblasts derived from αSMAtdTomato+
cells and the formation of reparative dentin devoid of osteoblasts provide in
vivo evidence for the stimulatory effects of FGF signaling on odontoblast differentiation
from early progenitors in dental pulp.
Publication Year: 2020
Publication Date: 2020-01-01
Language: en
Type: dissertation
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