The rescue of dentin matrix protein 1 (DMP1)-deficient tooth defects by the transgenic expression of dentin sialophosphoprotein (DSPP) indicates that DSPP is a downstream effector molecule of DMP1 in dentinogenesis.
Dentin matrix protein 1 (DMP1) and dentin sialophosphoprotein (DSPP) are essential for the formation of dentin. Previous in vitro studies have indicated that DMP1 might regulate the expression of DSPP during dentinogenesis. To examine whether DMP1 controls dentinogenesis through the regulation of DSPP in vivo, we cross-bred transgenic mice expressing normal DSPP driven by a 3.6-kb rat Col1a1 promoter with Dmp1 KO mice to generate mice expressing the DSPP transgene in the Dmp1 KO genetic background (referred to as "Dmp1 KO/DSPP Tg mice"). We used morphological, histological, and biochemical techniques to characterize the dentin and alveolar bone of Dmp1 KO/DSPP Tg mice compared with Dmp1 KO and wild-type mice. Our analyses showed that the expression of endogenous DSPP was remarkably reduced in the Dmp1 KO mice. Furthermore, the transgenic expression of DSPP rescued the tooth and alveolar bone defects of the Dmp1 KO mice. In addition, our in vitro analyses showed that DMP1 and its 57-kDa C-terminal fragment significantly up-regulated the Dspp promoter activities in a mesenchymal cell line. In contrast, the expression of DMP1 was not altered in the Dspp KO mice. These results provide strong evidence that DSPP is a downstream effector molecule that mediates the roles of DMP1 in dentinogenesis.
Department of Biomedical Sciences, Texas A&M Health Science Center, Baylor College of Dentistry, Dallas, Texas 75246, USA.
Monica Prasad
MP
Gibson
Qinglin
Q
Zhu
Suzhen
S
Wang
Qilin
Q
Liu
Ying
Y
Liu
Xiaofang
X
Wang
Baozhi
B
Yuan
L Bruno
LB
Ruest
Jian Q
JQ
Feng
Rena N
RN
D'Souza
Chunlin
C
Qin
Yongbo
Y
Lu
D000818:Animals; D058578:Biglycan / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D000090602:Collagen Type I, alpha 1 Chain; D003810:Dentinogenesis / Q000235:genetics*; D016326:Extracellular Matrix Proteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D008334:Mandible / Q000000981:diagnostic imaging / Q000254:growth & development / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009804:Odontoblasts / Q000166:cytology / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012795:Sialoglycoproteins / Q000235:genetics* / Q000378:metabolism; D014070:Tooth / Q000000981:diagnostic imaging / Q000254:growth & development / Q000378:metabolism; D014071:Tooth Abnormalities / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D055114:X-Ray Microtomography; D000099311:Dentin Sialophosphoprotein
D058578:Biglycan; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D016326:Extracellular Matrix Proteins; D018398:Homeodomain Proteins; D010750:Phosphoproteins; D012795:Sialoglycoproteins; D014157:Transcription Factors; D000099311:Dentin Sialophosphoprotein; C088334:Distal-less homeobox proteins; C513308:Dmp1 protein, mouse