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

• Published in: Scientific reports 2016-03, Vol.6 (1), p.23670-23670, Article 23670
• Main Authors: Liu, Jia, Saito, Kan, Maruya, Yuriko, Nakamura, Takashi, Yamada, Aya, Fukumoto, Emiko, Ishikawa, Momoko, Iwamoto, Tsutomu, Miyazaki, Kanako, Yoshizaki, Keigo, Ge, Lihong, Fukumoto, Satoshi
• Format: Article
• Language: English
• Subjects: 45/77; 631/136/142; 631/80/86/2368; 64/60; 96/106; 96/109; 96/95; Ameloblasts; Ameloblasts - cytology; Ameloblasts - metabolism; Amino Acid Sequence; Animals; Bone growth; Bone morphogenetic protein 2; Bone Morphogenetic Protein 2 - genetics; Bone Morphogenetic Protein 2 - metabolism; Cartilage diseases; Cell culture; Cell Differentiation; Chondrogenesis; Dental enamel; Dental Enamel - cytology; Dental Enamel - metabolism; Dental roots; Enamel; Gene expression; Gene Expression Regulation, Developmental; Growth differentiation factor 5; Growth Differentiation Factor 5 - genetics; Growth Differentiation Factor 5 - metabolism; Humanities and Social Sciences; Incisors; Mice; Mice, Inbred C57BL; Mice, Transgenic; Molars; multidisciplinary; Mutation; Odontogenesis - genetics; Osteoarthritis; Periodontal ligament; Phosphorylation; Rodents; Science; Sequence Alignment; Sequence Homology, Amino Acid; Signal Transduction; Smad1 Protein - genetics; Smad1 Protein - metabolism; Smad5 Protein - genetics; Smad5 Protein - metabolism; Smad8 Protein - genetics; Smad8 Protein - metabolism; Teeth
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep23670

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.