title: Reduced Dentin Matrix Protein Expression in Camurati-Engelmann Disease Transgenic Mouse Model.
abstract: 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.
authors.affiliation: Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama.|Institute of Oral Health Research, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Angela
authors.initials: A
authors.lastname: Gullard
authors.affiliation: Institute of Oral Health Research, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Christina M
authors.initials: CM
authors.lastname: Croney
authors.affiliation: Department of Surgery, School of Medicine, Shihezi University, Shihezi, Xinjiang, China.
authors.forename: Xiangwei
authors.initials: X
authors.lastname: Wu
authors.affiliation: Institute of Oral Health Research, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Olga
authors.initials: O
authors.lastname: Mamaeva
authors.affiliation: Institute of Oral Health Research, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Philip
authors.initials: P
authors.lastname: Sohn
authors.affiliation: Department of Orthopaedic Surgery, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Xu
authors.initials: X
authors.lastname: Cao
authors.affiliation: Institute of Oral Health Research, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Mary
authors.initials: M
authors.lastname: MacDougall
mesh_terms: D000818:Animals; D015153:Blotting, Western; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D002113:Calcification, Physiologic; D003966:Camurati-Engelmann Syndrome / Q000378:metabolism*; D049109:Cell Proliferation; D002478:Cells, Cultured; D003782:Dental Pulp / Q000166:cytology; D003804:Dentin / Q000378:metabolism*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D021621:Imaging, Three-Dimensional; D007150:Immunohistochemistry; D007700:Kinetics; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008963:Molar / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D055114:X-Ray Microtomography
chemical_list: D019485:Bone Morphogenetic Proteins; D016212:Transforming Growth Factor beta