TY - JOUR
T1 - Reduced Dentin Matrix Protein Expression in Camurati-Engelmann Disease Transgenic Mouse Model
AU - Gullard, Angela
AU - Croney, Christina M.
AU - Wu, Xiangwei
AU - Mamaeva, Olga
AU - Sohn, Philip
AU - Cao, Xu
AU - Macdougall, Mary
N1 - Publisher Copyright:
© 2015 Wiley Periodicals, Inc.
PY - 2016/5/1
Y1 - 2016/5/1
N2 - Overexpression of transforming growth factor-β1 (TGF-β1) has been shown to lead to mineralization defects in both the enamel and dentin layers of teeth. A TGFB1 point mutation (H222D), derived from published cases of Camurati-Engelmann disease (CED), has been shown to constitutively activate TGF-β1, leading to excess bone matrix production. Although CED has been well documented in clinical case reports, there are no published studies on the effect of CED on the dentition. The objective of this study was to determine the dental manifestations of hyperactivated TGF-β1 signaling using an established mouse model of CED-derived TGF-β1 mutation. Murine dental tissues were studied via radiography, micro-CT, immunohistochemistry, and qRT-PCR. Results showed that initial decreased dental mineralized tissue density is resolved. Proliferation assays of incisor pulp and alveolar bone cell cultures revealed that cells from transgenic animals displayed a reduced rate of growth compared to alveolar bone cultures from wild-type mice. TGF-β family gene expression analysis indicated significant fold changes in the expression of Alpl, Bmp2-5, Col-1, -2, -4, and -6, Fgf, Mmp, Runx2, Tgfb3, Tfgbr3, and Vdr genes. Assessment of SIBLINGs revealed downregulation of Ibsp, Dmp1, Dspp, Mepe, and Spp1, as well as reduced staining for BMP-2 and VDR in mesenchymal-derived pulp tissue in CED animals. Treatment of dental pulp cells with recombinant human TGF-β1 resulted in increased SIBLING gene expression. Conclusions: Our results provide in vivo evidence suggesting that TFG-β1 mediates expression of important dentin extracellular matrix components secreted by dental pulp, and when unbalanced, may contribute to abnormal dentin disorders.
AB - Overexpression of transforming growth factor-β1 (TGF-β1) has been shown to lead to mineralization defects in both the enamel and dentin layers of teeth. A TGFB1 point mutation (H222D), derived from published cases of Camurati-Engelmann disease (CED), has been shown to constitutively activate TGF-β1, leading to excess bone matrix production. Although CED has been well documented in clinical case reports, there are no published studies on the effect of CED on the dentition. The objective of this study was to determine the dental manifestations of hyperactivated TGF-β1 signaling using an established mouse model of CED-derived TGF-β1 mutation. Murine dental tissues were studied via radiography, micro-CT, immunohistochemistry, and qRT-PCR. Results showed that initial decreased dental mineralized tissue density is resolved. Proliferation assays of incisor pulp and alveolar bone cell cultures revealed that cells from transgenic animals displayed a reduced rate of growth compared to alveolar bone cultures from wild-type mice. TGF-β family gene expression analysis indicated significant fold changes in the expression of Alpl, Bmp2-5, Col-1, -2, -4, and -6, Fgf, Mmp, Runx2, Tgfb3, Tfgbr3, and Vdr genes. Assessment of SIBLINGs revealed downregulation of Ibsp, Dmp1, Dspp, Mepe, and Spp1, as well as reduced staining for BMP-2 and VDR in mesenchymal-derived pulp tissue in CED animals. Treatment of dental pulp cells with recombinant human TGF-β1 resulted in increased SIBLING gene expression. Conclusions: Our results provide in vivo evidence suggesting that TFG-β1 mediates expression of important dentin extracellular matrix components secreted by dental pulp, and when unbalanced, may contribute to abnormal dentin disorders.
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U2 - 10.1002/jcp.25207
DO - 10.1002/jcp.25207
M3 - Article
C2 - 26427011
AN - SCOPUS:84956668726
SN - 0021-9541
VL - 231
SP - 1106
EP - 1113
JO - Journal of Cellular Physiology
JF - Journal of Cellular Physiology
IS - 5
ER -