title: Correlation between Fibrillin-1 Degradation and mRNA Downregulation and Myofibroblast Differentiation in Cultured Human Dental Pulp Tissue.
abstract: Myofibroblasts and extracellular matrix are important components in wound healing. Alpha-smooth muscle actin (α-SMA) is a marker of myofibroblasts. Fibrillin-1 is a major constituent of microfibrils and an extracellular-regulator of TGF-β1, an important cytokine in the transdifferentiation of resident fibroblasts into myofibroblasts. To study the correlation between changes in fibrillin-1 expression and myofibroblast differentiation, we examined alterations in fibrillin-1 and α-SMA expression in organotypic cultures of dental pulp in vitro. Extracted healthy human teeth were cut to 1-mm-thick slices and cultured for 7 days. In intact dental pulp, fibrillin-1 was broadly distributed, and α-SMA was observed in pericytes and vascular smooth muscle cells. After 7 days of culture, immunostaining for fibrillin-1 became faint concomitant with a downregulation in its mRNA levels. Furthermore, fibroblasts, odontoblasts and Schwann cells were immunoreactive for α-SMA with a significant increase in α-SMA mRNA expression. Double immunofluorescence staining was positive for pSmad2/3, central mediators of TGF-β signaling, and α-SMA. The administration of inhibitors for extracellular matrix proteases recovered fibrillin-1 immunostaining; moreover, fibroblasts lost their immunoreactivity for α-SMA along with a downregulation in α-SMA mRNA. These findings suggest that the expression of α-SMA is TGF-β1 dependent, and fibrillin-1 degradation and downregulation might be implicated in the differentiation of myofibroblasts in dental pulp wound healing.
authors: Division of Cariology, Operative Dentistry and Endodontics, Department of Oral Health Science, Course for Oral Life Science Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan (NY, KY, NO, ET, NE, TO)
authors: Nagako
authors: N
authors: Yoshiba
authors: Division of Cariology, Operative Dentistry and Endodontics, Department of Oral Health Science, Course for Oral Life Science Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan (NY, KY, NO, ET, NE, TO)
authors: Kunihiko
authors: K
authors: Yoshiba
authors: Division of Cariology, Operative Dentistry and Endodontics, Department of Oral Health Science, Course for Oral Life Science Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan (NY, KY, NO, ET, NE, TO)
authors: Naoto
authors: N
authors: Ohkura
authors: Division of Cariology, Operative Dentistry and Endodontics, Department of Oral Health Science, Course for Oral Life Science Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan (NY, KY, NO, ET, NE, TO)
authors: Erika
authors: E
authors: Takei
authors: Division of Cariology, Operative Dentistry and Endodontics, Department of Oral Health Science, Course for Oral Life Science Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan (NY, KY, NO, ET, NE, TO)
authors: Naoki
authors: N
authors: Edanami
authors: Division of Reconstructive Surgery for Oral and Maxillofacial Region, Department of Oral Health Science, Course for Oral Life Science Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan(YO)
authors: Youhei
authors: Y
authors: Oda
authors: Department of Oral Histology, Institute for Dental Science, Matsumoto Dental University, Shiojiri, Nagano, Japan (AH, HN)
authors: Akihiro
authors: A
authors: Hosoya
authors: Department of Oral Histology, Institute for Dental Science, Matsumoto Dental University, Shiojiri, Nagano, Japan (AH, HN)
authors: Hiroaki
authors: H
authors: Nakamura
authors: Division of Cariology, Operative Dentistry and Endodontics, Department of Oral Health Science, Course for Oral Life Science Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan (NY, KY, NO, ET, NE, TO)
authors: Takashi
authors: T
authors: Okiji
mesh_terms: D000199:Actins / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D002454:Cell Differentiation; D002478:Cells, Cultured; D003782:Dental Pulp / Q000166:cytology*; D015536:Down-Regulation; D000071838:Fibrillin-1; D000071837:Fibrillins; D006801:Humans; D008840:Microfilament Proteins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism*; D058628:Myofibroblasts / Q000166:cytology* / Q000378:metabolism; D059748:Proteolysis; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics*; D051899:Smad2 Protein / Q000032:analysis; D051900:Smad3 Protein / Q000032:analysis; D053773:Transforming Growth Factor beta1 / Q000235:genetics; D055815:Young Adult; D054392:Adipokines
chemical_list: D000199:Actins; D000071838:Fibrillin-1; D000071837:Fibrillins; D008840:Microfilament Proteins; D012333:RNA, Messenger; D051899:Smad2 Protein; D051900:Smad3 Protein; D053773:Transforming Growth Factor beta1; C000605722:FBN1 protein, human; D054392:Adipokines
keywords: culture; fibrillin-1; human dental pulp; pSmad2/3; α-SMA