TGF-beta3 induces ectopic mineralization in fetal mouse dental pulp during tooth germ development.
Several members of the transforming growth factor (TGF)-beta superfamily are expressed in developing teeth from the initiation stage through adulthood. Of those, TGF-beta1 regulates odontoblast differentiation and dentin extracellular matrix synthesis. However, the molecular mechanism of TGF-beta3 in dental pulp cells is not clearly understood. In the present study, beads soaked with human recombinant TGF-beta3 induced ectopic mineralization in dental pulp from fetal mouse tooth germ samples, which increased in a dose-dependent manner. Further, TGF-beta3 promoted mRNA expression, and increased protein levels of osteocalcin (OCN) and type I collagen (COL I) in dental pulp cells. We also observed that the expression of dentin sialophosphoprotein and dentin matrix protein 1 was induced by TGF-beta3 in primary cultured dental pulp cells, however, not in calvaria osteoblasts, whereas OCN, osteopontin and osteonectin expression was increased after treatment with TGF-beta3 in both dental pulp cells and calvaria osteoblasts. Dentin sialoprotein was also partially detected in the vicinity of TGF-beta3 soaked beads in vivo. These results indicate for the first time that TGF-beta3 induces ectopic mineralization through upregulation of OCN and COL I expression in dental pulp cells, and may regulate the differentiation of dental pulp stem cells to odontoblasts.
Huojia
Muhetaer
M
Division of Maxillofacial Diagnostic and Surgical Science, Faculty of Dental Science, Kyushu University, Higashi-Ku, Fukuoka 812-8582, Japan.
Muraoka
Noriko
N
Yoshizaki
Keigo
K
Fukumoto
Satoshi
S
Nakashima
Misako
M
Akamine
Akifumi
A
Nonaka
Kazuaki
K
Ohishi
Masamichi
M
D000818:Animals; D000880:Anthraquinones; D024042:Collagen Type I / Q000378:metabolism; D017931:DNA Primers; D003782:Dental Pulp / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D008863:Microspheres; D008963:Molar / Q000196:embryology*; D015675:Osteocalcin / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012795:Sialoglycoproteins / Q000378:metabolism; D014074:Tooth Calcification / Q000187:drug effects*; D016212:Transforming Growth Factor beta / Q000378:metabolism / Q000494:pharmacology*; D053782:Transforming Growth Factor beta3
D000880:Anthraquinones; D024042:Collagen Type I; D017931:DNA Primers; D012795:Sialoglycoproteins; C509045:Tgfb3 protein, mouse; D016212:Transforming Growth Factor beta; D053782:Transforming Growth Factor beta3; D015675:Osteocalcin; C004468:Alizarin Red S