Abstract
Tissue regeneration and development involves highly synchronized signals both between cells and with the extracellular environment. Biomaterials can be tuned to mimic specific biological signals and control cell response(s). As a result, these materials can be used as tools to elucidate cell signaling pathways and candidate molecules involved with cellular processes. In this work, we explore enamel-forming cells, ameloblasts, which have a limited regenerative capacity. By exposing undifferentiated cells to a self-assembling matrix bearing RGDS epitopes, we elicited a regenerative signal at will that subsequently led to the identification of thrombospondin 2 (TSP2), an extracellular matrix protein that has not been previously recognized as a key player in enamel development and regeneration. Targeted disruption of the thrombospondin 2 gene (. Thbs2) resulted in enamel formation with a disordered architecture that was highly susceptible to wear compared to their wild-type counterparts. To test the regenerative capacity, we injected the bioactive matrix into the enamel organ and discovered that the enamel organic epithelial cells in TSP-null mice failed to polarize on the surface of the artificial matrix, greatly reducing integrin β1 and Notch1 expression levels, which represent signaling pathways known to be associated with TSP2. These results suggest TSP2 plays an important role in regulating cell-matrix interactions during enamel formation. Exploiting the signaling pathways activated by biomaterials can provide insight into native signaling mechanisms crucial for tooth development and cell-based strategies for enamel regeneration.
| Original language | English |
|---|---|
| Pages (from-to) | 216-228 |
| Number of pages | 13 |
| Journal | Biomaterials |
| Volume | 61 |
| DOIs | |
| Publication status | Published - Aug 1 2015 |
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Keywords
- Enamel regeneration
- Nano-fabricated artificial matrix
- Peptide amphiphile
- Signaling pathway
- Thrombospondin 2
ASJC Scopus subject areas
- Biomaterials
- Bioengineering
- Ceramics and Composites
- Mechanics of Materials
- Biophysics
Cite this
Bioactive nanofibers enable the identification of thrombospondin 2 as a key player in enamel regeneration. / Huang, Zhan; Newcomb, Christina J.; Lei, Yaping; Zhou, Yan; Bornstein, Paul; Amendt, Brad A.; Stupp, Samuel I; Snead, Malcolm L.
In: Biomaterials, Vol. 61, 01.08.2015, p. 216-228.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Bioactive nanofibers enable the identification of thrombospondin 2 as a key player in enamel regeneration
AU - Huang, Zhan
AU - Newcomb, Christina J.
AU - Lei, Yaping
AU - Zhou, Yan
AU - Bornstein, Paul
AU - Amendt, Brad A.
AU - Stupp, Samuel I
AU - Snead, Malcolm L.
PY - 2015/8/1
Y1 - 2015/8/1
N2 - Tissue regeneration and development involves highly synchronized signals both between cells and with the extracellular environment. Biomaterials can be tuned to mimic specific biological signals and control cell response(s). As a result, these materials can be used as tools to elucidate cell signaling pathways and candidate molecules involved with cellular processes. In this work, we explore enamel-forming cells, ameloblasts, which have a limited regenerative capacity. By exposing undifferentiated cells to a self-assembling matrix bearing RGDS epitopes, we elicited a regenerative signal at will that subsequently led to the identification of thrombospondin 2 (TSP2), an extracellular matrix protein that has not been previously recognized as a key player in enamel development and regeneration. Targeted disruption of the thrombospondin 2 gene (. Thbs2) resulted in enamel formation with a disordered architecture that was highly susceptible to wear compared to their wild-type counterparts. To test the regenerative capacity, we injected the bioactive matrix into the enamel organ and discovered that the enamel organic epithelial cells in TSP-null mice failed to polarize on the surface of the artificial matrix, greatly reducing integrin β1 and Notch1 expression levels, which represent signaling pathways known to be associated with TSP2. These results suggest TSP2 plays an important role in regulating cell-matrix interactions during enamel formation. Exploiting the signaling pathways activated by biomaterials can provide insight into native signaling mechanisms crucial for tooth development and cell-based strategies for enamel regeneration.
AB - Tissue regeneration and development involves highly synchronized signals both between cells and with the extracellular environment. Biomaterials can be tuned to mimic specific biological signals and control cell response(s). As a result, these materials can be used as tools to elucidate cell signaling pathways and candidate molecules involved with cellular processes. In this work, we explore enamel-forming cells, ameloblasts, which have a limited regenerative capacity. By exposing undifferentiated cells to a self-assembling matrix bearing RGDS epitopes, we elicited a regenerative signal at will that subsequently led to the identification of thrombospondin 2 (TSP2), an extracellular matrix protein that has not been previously recognized as a key player in enamel development and regeneration. Targeted disruption of the thrombospondin 2 gene (. Thbs2) resulted in enamel formation with a disordered architecture that was highly susceptible to wear compared to their wild-type counterparts. To test the regenerative capacity, we injected the bioactive matrix into the enamel organ and discovered that the enamel organic epithelial cells in TSP-null mice failed to polarize on the surface of the artificial matrix, greatly reducing integrin β1 and Notch1 expression levels, which represent signaling pathways known to be associated with TSP2. These results suggest TSP2 plays an important role in regulating cell-matrix interactions during enamel formation. Exploiting the signaling pathways activated by biomaterials can provide insight into native signaling mechanisms crucial for tooth development and cell-based strategies for enamel regeneration.
KW - Enamel regeneration
KW - Nano-fabricated artificial matrix
KW - Peptide amphiphile
KW - Signaling pathway
KW - Thrombospondin 2
UR - http://www.scopus.com/inward/record.url?scp=84939198462&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84939198462&partnerID=8YFLogxK
U2 - 10.1016/j.biomaterials.2015.05.035
DO - 10.1016/j.biomaterials.2015.05.035
M3 - Article
C2 - 26004236
AN - SCOPUS:84939198462
VL - 61
SP - 216
EP - 228
JO - Biomaterials
JF - Biomaterials
SN - 0142-9612
ER -