The mammalian periodontium is a unique support structure that anchors teeth in the jaw bone by providing firm attachment and resilient responsiveness to pressures. Much of the resilient properties of the periodontium are facilitated by a non-mineralized periodontal ligament (PDL) that connects the root surface with the alveolar bone. Recent studies from our laboratory have suggested that ameloblastin (AMBN) was 300-fold upregulated during periodontal remodeling (Holliday et al. 2005, Luan et al. 2007). In addition, we have localized AMBN in Hertwig's Epithelial Root Sheath (HERS) and revealed an inhibitory effect of AMBN on PDL mineralization and crystal formation in solution and gels. Our K14 promoter-driven, AMBN overexpressing transgenic mouse model featured a robust periodontal phenotype with changes in root cementum surface structure, cervical alveolar bone height, periodontal ligament width, and altered enamel structure compared to wild-type controls. Our findings were underscored by clinical studies that have shown a positive effect of enamel matrix derivatives (EMD) on the prevention of ankylosis (Iqbal and Bamaas 2001, Filippi et al. 2001) and by ameloblastin and amelogenin gene knockout models displaying evidence of PDL hypercalcification (Fukomoto et al. 2004, Hatakeyama et al. 2006). Together, these preliminary studies provide the basis for a research plan in which we will address the question whether AMBN is a unique HERS product involved in periodontal development and mineral homeostasis. Proposed studies are designed to explore and develop novel clinical aids to the benefit of Millions of Americans suffering from periodontal disease. ? ?

Public Health Relevance

One of the most unique features of tooth gums is the elastic but firm attachment of tooth roots to the jaw bone. Here we will conduct a series of studies to investigate the effect of a unique gene product (called ameloblastin) in the formation of tooth attachment. These studies might eventually lead to novel cures for gum diseases. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
1R01DE019155-01
Application #
7507570
Study Section
Special Emphasis Panel (ZRG1-MOSS-K (09))
Program Officer
Lumelsky, Nadya L
Project Start
2008-08-01
Project End
2013-06-30
Budget Start
2008-08-01
Budget End
2009-06-30
Support Year
1
Fiscal Year
2008
Total Cost
$370,685
Indirect Cost
Name
University of Illinois at Chicago
Department
Dentistry
Type
Schools of Dentistry
DUNS #
098987217
City
Chicago
State
IL
Country
United States
Zip Code
60612
Lu, Xuanyu; Fukumoto, Satoshi; Yamada, Yoshihiko et al. (2016) Ameloblastin, an Extracellular Matrix Protein, Affects Long Bone Growth and Mineralization. J Bone Miner Res 31:1235-46
Lu, Xuanyu; Li, Wenjin; Fukumoto, Satoshi et al. (2016) The ameloblastin extracellular matrix molecule enhances bone fracture resistance and promotes rapid bone fracture healing. Matrix Biol 52-54:113-126
Atsawasuwan, P; Lu, X; Ito, Y et al. (2013) Expression and function of enamel-related gene products in calvarial development. J Dent Res 92:622-8
Lu, Xuanyu; Ito, Yoshihiro; Atsawasuwan, Phimon et al. (2013) Ameloblastin modulates osteoclastogenesis through the integrin/ERK pathway. Bone 54:157-168
Atsawasuwan, Phimon; Lu, Xuanyu; Ito, Yoshihiro et al. (2013) Ameloblastin inhibits cranial suture closure by modulating MSX2 expression and proliferation. PLoS One 8:e52800
Dangaria, Smit J; Ito, Yoshihiro; Yin, LeiLei et al. (2011) Apatite microtopographies instruct signaling tapestries for progenitor-driven new attachment of teeth. Tissue Eng Part A 17:279-90
Zhang, Youbin; Zhang, Xu; Lu, Xuanyu et al. (2011) Ameloblastin regulates cell attachment and proliferation through RhoA and p27. Eur J Oral Sci 119 Suppl 1:280-5
Lu, Xuanyu; Ito, Yoshihiro; Kulkarni, Ashok et al. (2011) Ameloblastin-rich enamel matrix favors short and randomly oriented apatite crystals. Eur J Oral Sci 119 Suppl 1:254-60
Zhang, Xu; Diekwisch, Thomas G H; Luan, Xianghong (2011) Structure and function of ameloblastin as an extracellular matrix protein: adhesion, calcium binding, and CD63 interaction in human and mouse. Eur J Oral Sci 119 Suppl 1:270-9
Dangaria, Smit Jayant; Ito, Yoshihiro; Luan, Xianghong et al. (2011) Successful periodontal ligament regeneration by periodontal progenitor preseeding on natural tooth root surfaces. Stem Cells Dev 20:1659-68

Showing the most recent 10 out of 15 publications