Tenomodulin expresses during development of periodontal ligament and enhance cellular adhesion.

2011 Fiscal Year Final Research Report

• Project/Area Number: 22890047
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Orthodontic/Pediatric dentistry
• Research Institution: The University of Tokyo
• Principal Investigator: KOMIYAMA Yusuke 東京大学, 医学部附属病院, 特認臨床医 (90586471)
• Project Period (FY): 2010 – 2011
• Keywords: 歯周靭帯 / Tenomodulin / リモデリング / 細胞高次機能 / 再生医学 / 歯科矯正学 / 細胞接着 / 細胞形態

Research Abstract

Objectives : This study aimed to investigate the expression of tenomodulin(Tnmd) during murine tooth eruption and explore its biological function in vitro.
Methods : Specific antibodies against murine Tnmd were established. Expression of Tnmd during the three eruption phases(pre-eruptive, eruptive or post-eruptive phase) of murine molars was determined by immunohistochemistry in wild type(WT) or Tnmd knockout(KO) mice specimens. To determine roles of Tnmd in cell adhesion, cell adhesion assay was performed in NIH3T3 cells transfected with Tnmd or its extracellular domain deletion mutants.
Results : The specificity of the Tnmd-antibody was confirmed by immunohistochemistry of WT or Tnmd KO mice tail tendons. This antibody revealed the expression of Tnmd in periodontal ligament ; the Tnmd expression was increased at eruptive phase and sustained after eruption. Given that dental attrition was observed in eruptive and post-eruptive phases, teeth were likely exposed to occlusal forces at these time points. Functional analyses in vitro revealed that Tnmd overexpression resulted in enhancement of cell adhesion in NIH3T3 cells. The enhancement was confirmed in fibroblasts derived from WT or Tnmd KO mice. Deletion of cleavage site or BRICHOS domain diminished cell adhesion, whereas deletion of C-terminal domain(CTD) retained the positive effect on cell adhesion. The result suggests that BRICHOS domain, but not CTD, is responsible for the Tnmd-mediated enhancement of cell adhesion.
Conclution : Expression of Tnmd was correlated with the time of eruption when occlusal force was transferred to teeth and surrounding tissues. This observation suggests that the regulation of Tnmd expression may be controlled partially by mechanical forces in dense connective tissues. In addition, Tnmd is likely to have positive effects on cell adhesion. Further analyses will reveal the regulation of Tnmd expression and its function in more detail.