Nuclear factor I-C is essential for odontogenic cell proliferation and odontoblast differentiation during tooth root development.
Our previous studies have demonstrated that nuclear factor I-C (NFI-C) null mice developed short molar roots that contain aberrant odontoblasts and abnormal dentin formation. Based on these findings, we performed studies to elucidate the function of NFI-C in odontoblasts. Initial studies demonstrated that aberrant odontoblasts become dissociated and trapped in an osteodentin-like mineralized tissue. Abnormal odontoblasts exhibit strong bone sialoprotein expression but a decreased level of dentin sialophosphoprotein expression when compared with wild type odontoblasts. Loss of Nfic results in an increase in p-Smad2/3 expression in aberrant odontoblasts and pulp cells in the subodontoblastic layer in vivo and primary pulp cells from Nfic-deficient mice in vitro. Cell proliferation analysis of both cervical loop and ectomesenchymal cells of the Nfic-deficient mice revealed significantly decreased proliferative activity compared with wild type mice. In addition, Nfic-deficient primary pulp cells showed increased expression of p21 and p16 but decreased expression of cyclin D1 and cyclin B1, strongly suggesting cell growth arrest caused by a lack of Nfic activity. Analysis of the pulp and abnormal dentin in Nfic-deficient mice revealed an increase in apoptotic activity. Further, Nfic-deficient primary pulp cells exhibited an increase in caspase-8 and -3 activation, whereas the cleaved form of Bid was hardly detected. These results indicate that the loss of Nfic leads to the suppression of odontogenic cell proliferation and differentiation and induces apoptosis of aberrant odontoblasts during root formation, thereby contributing to the formation of short roots.
Lee
Dong-Seol
DS
From the Department of Oral Histology-Developmental Biology, Dental Research Institute, Seoul 110-749, Korea.
Park
Jong-Tae
JT
From the Department of Oral Histology-Developmental Biology, Dental Research Institute, Seoul 110-749, Korea.
Kim
Hyun-Man
HM
From the Department of Oral Histology-Developmental Biology, Dental Research Institute, Seoul 110-749, Korea.
Ko
Jea Seung
JS
From the Department of Oral Histology-Developmental Biology, Dental Research Institute, Seoul 110-749, Korea.
Son
Ho-Hyun
HH
Conservative Dentistry, Seoul 110-749, Korea.
Gronostajski
Richard M
RM
Department of Biochemistry and the Program in Neuroscience, School of Medicine and Biomedical Science, Buffalo, New York 14214-3092.
Cho
Moon-Il
MI
Department of Oral Biology, School of Dental Medicine, State University of New York at Buffalo, Buffalo, New York 14214-3092.
Choung
Pill-Hoon
PH
Oral & Maxillofacial Surgery, Seoul 110-749, Korea; Tooth Bioengineering National Research Lab, School of Dentistry, Seoul National University, Seoul 110-749, Korea.
Park
Joo-Cheol
JC
From the Department of Oral Histology-Developmental Biology, Dental Research Institute, Seoul 110-749, Korea. Electronic address: jcapark@snu.ac.kr.
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D017931:DNA Primers / Q000235:genetics; D003804:Dentin / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D051839:NFI Transcription Factors / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D009804:Odontoblasts / Q000166:cytology* / Q000378:metabolism*; D009805:Odontogenesis / Q000235:genetics / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D034622:RNA Interference; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D051899:Smad2 Protein / Q000378:metabolism; D051900:Smad3 Protein / Q000378:metabolism; D014092:Tooth Root / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism*
D017931:DNA Primers; D051839:NFI Transcription Factors; D018125:Receptors, Transforming Growth Factor beta; D051899:Smad2 Protein; C497783:Smad2 protein, mouse; D051900:Smad3 Protein; C497791:Smad3 protein, mouse; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I