Mutant GDF5 enhances ameloblast differentiation via accelerated BMP2-induced Smad1/5/8 phosphorylation

Jia Liu, Kan Saito, Yuriko Maruya, Takashi Nakamura, Aya Yamada, Emiko Fukumoto, Momoko Ishikawa, Tsutomu Iwamoto, Kanako Miyazaki, Keigo Yoshizaki, Lihong Ge, Satoshi Fukumoto

研究成果: ジャーナルへの寄稿記事

5 引用 (Scopus)

抄録

Bone morphogenetic proteins (BMPs) regulate hard tissue formation, including bone and tooth. Growth differentiation factor 5 (GDF5), a known BMP, is expressed in cartilage and regulates chondrogenesis, and mutations have been shown to cause osteoarthritis. Notably, GDF5 is also expressed in periodontal ligament tissue; however, its role during tooth development is unclear. Here, we used cell culture and in vivo analyses to determine the role of GDF5 during tooth development. GDF5 and its associated BMP receptors are expressed at the protein and mRNA levels during postnatal tooth development, particularly at a stage associated with enamel formation. Furthermore, whereas BMP2 was observed to induce evidently the differentiation of enamel-forming ameloblasts, excess GDF5 induce mildly this differentiation. A mouse model harbouring a mutation in GDF5 (W408R) showed enhanced enamel formation in both the incisors and molars, but not in the tooth roots. Overexpression of the W408R GDF5 mutant protein was shown to induce BMP2-mediated mRNA expression of enamel matrix proteins and downstream phosphorylation of Smad1/5/8. These results suggest that mutant GDF5 enhances ameloblast differentiation via accelerated BMP2-signalling.

元の言語英語
記事番号23670
ジャーナルScientific reports
6
DOI
出版物ステータス出版済み - 3 31 2016

Fingerprint

Growth Differentiation Factor 5
Ameloblasts
Phosphorylation
Tooth
Dental Enamel
Bone Morphogenetic Proteins
Bone Morphogenetic Protein Receptors
Tooth Root
Chondrogenesis
Periodontal Ligament
Messenger RNA
Mutation
Mutant Proteins
Incisor
Osteogenesis
Osteoarthritis
Cartilage
Cell Culture Techniques

All Science Journal Classification (ASJC) codes

  • General

これを引用

Mutant GDF5 enhances ameloblast differentiation via accelerated BMP2-induced Smad1/5/8 phosphorylation. / Liu, Jia; Saito, Kan; Maruya, Yuriko; Nakamura, Takashi; Yamada, Aya; Fukumoto, Emiko; Ishikawa, Momoko; Iwamoto, Tsutomu; Miyazaki, Kanako; Yoshizaki, Keigo; Ge, Lihong; Fukumoto, Satoshi.

:: Scientific reports, 巻 6, 23670, 31.03.2016.

研究成果: ジャーナルへの寄稿記事

Liu, Jia ; Saito, Kan ; Maruya, Yuriko ; Nakamura, Takashi ; Yamada, Aya ; Fukumoto, Emiko ; Ishikawa, Momoko ; Iwamoto, Tsutomu ; Miyazaki, Kanako ; Yoshizaki, Keigo ; Ge, Lihong ; Fukumoto, Satoshi. / Mutant GDF5 enhances ameloblast differentiation via accelerated BMP2-induced Smad1/5/8 phosphorylation. :: Scientific reports. 2016 ; 巻 6.
@article{1fd11e7366154898b836b27fc83b5f93,
title = "Mutant GDF5 enhances ameloblast differentiation via accelerated BMP2-induced Smad1/5/8 phosphorylation",
abstract = "Bone morphogenetic proteins (BMPs) regulate hard tissue formation, including bone and tooth. Growth differentiation factor 5 (GDF5), a known BMP, is expressed in cartilage and regulates chondrogenesis, and mutations have been shown to cause osteoarthritis. Notably, GDF5 is also expressed in periodontal ligament tissue; however, its role during tooth development is unclear. Here, we used cell culture and in vivo analyses to determine the role of GDF5 during tooth development. GDF5 and its associated BMP receptors are expressed at the protein and mRNA levels during postnatal tooth development, particularly at a stage associated with enamel formation. Furthermore, whereas BMP2 was observed to induce evidently the differentiation of enamel-forming ameloblasts, excess GDF5 induce mildly this differentiation. A mouse model harbouring a mutation in GDF5 (W408R) showed enhanced enamel formation in both the incisors and molars, but not in the tooth roots. Overexpression of the W408R GDF5 mutant protein was shown to induce BMP2-mediated mRNA expression of enamel matrix proteins and downstream phosphorylation of Smad1/5/8. These results suggest that mutant GDF5 enhances ameloblast differentiation via accelerated BMP2-signalling.",
author = "Jia Liu and Kan Saito and Yuriko Maruya and Takashi Nakamura and Aya Yamada and Emiko Fukumoto and Momoko Ishikawa and Tsutomu Iwamoto and Kanako Miyazaki and Keigo Yoshizaki and Lihong Ge and Satoshi Fukumoto",
year = "2016",
month = "3",
day = "31",
doi = "10.1038/srep23670",
language = "English",
volume = "6",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Mutant GDF5 enhances ameloblast differentiation via accelerated BMP2-induced Smad1/5/8 phosphorylation

AU - Liu, Jia

AU - Saito, Kan

AU - Maruya, Yuriko

AU - Nakamura, Takashi

AU - Yamada, Aya

AU - Fukumoto, Emiko

AU - Ishikawa, Momoko

AU - Iwamoto, Tsutomu

AU - Miyazaki, Kanako

AU - Yoshizaki, Keigo

AU - Ge, Lihong

AU - Fukumoto, Satoshi

PY - 2016/3/31

Y1 - 2016/3/31

N2 - Bone morphogenetic proteins (BMPs) regulate hard tissue formation, including bone and tooth. Growth differentiation factor 5 (GDF5), a known BMP, is expressed in cartilage and regulates chondrogenesis, and mutations have been shown to cause osteoarthritis. Notably, GDF5 is also expressed in periodontal ligament tissue; however, its role during tooth development is unclear. Here, we used cell culture and in vivo analyses to determine the role of GDF5 during tooth development. GDF5 and its associated BMP receptors are expressed at the protein and mRNA levels during postnatal tooth development, particularly at a stage associated with enamel formation. Furthermore, whereas BMP2 was observed to induce evidently the differentiation of enamel-forming ameloblasts, excess GDF5 induce mildly this differentiation. A mouse model harbouring a mutation in GDF5 (W408R) showed enhanced enamel formation in both the incisors and molars, but not in the tooth roots. Overexpression of the W408R GDF5 mutant protein was shown to induce BMP2-mediated mRNA expression of enamel matrix proteins and downstream phosphorylation of Smad1/5/8. These results suggest that mutant GDF5 enhances ameloblast differentiation via accelerated BMP2-signalling.

AB - Bone morphogenetic proteins (BMPs) regulate hard tissue formation, including bone and tooth. Growth differentiation factor 5 (GDF5), a known BMP, is expressed in cartilage and regulates chondrogenesis, and mutations have been shown to cause osteoarthritis. Notably, GDF5 is also expressed in periodontal ligament tissue; however, its role during tooth development is unclear. Here, we used cell culture and in vivo analyses to determine the role of GDF5 during tooth development. GDF5 and its associated BMP receptors are expressed at the protein and mRNA levels during postnatal tooth development, particularly at a stage associated with enamel formation. Furthermore, whereas BMP2 was observed to induce evidently the differentiation of enamel-forming ameloblasts, excess GDF5 induce mildly this differentiation. A mouse model harbouring a mutation in GDF5 (W408R) showed enhanced enamel formation in both the incisors and molars, but not in the tooth roots. Overexpression of the W408R GDF5 mutant protein was shown to induce BMP2-mediated mRNA expression of enamel matrix proteins and downstream phosphorylation of Smad1/5/8. These results suggest that mutant GDF5 enhances ameloblast differentiation via accelerated BMP2-signalling.

UR - http://www.scopus.com/inward/record.url?scp=84962911714&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84962911714&partnerID=8YFLogxK

U2 - 10.1038/srep23670

DO - 10.1038/srep23670

M3 - Article

C2 - 27030100

AN - SCOPUS:84962911714

VL - 6

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

M1 - 23670

ER -