2. Academic Validation
  3. Metabotropic glutamate receptor 1 promotes cementoblast proliferation via MAP kinase signaling pathways

Metabotropic glutamate receptor 1 promotes cementoblast proliferation via MAP kinase signaling pathways

  • Connect Tissue Res. 2016 Sep;57(5):417-26. doi: 10.1080/03008207.2016.1195826.
Sousuke Kanaya 1 2,  Hidehiro Komatsu 1,  Hidetoshi Shimauchi 1,  Eiji Nemoto 1
Affiliations

Affiliations

  • 1 a Department of Periodontology and Endodontology , Tohoku University Graduate School of Dentistry , Sendai , Japan.
  • 2 b Liaison Center for Innovative Dentistry , Graduate School of Dentistry, Tohoku University , Sendai , Japan.
PMID: 27261070 DOI: 10.1080/03008207.2016.1195826
Abstract

Purpose/aim: Glutamate is one of the signaling molecules responsible for transmission in the central nervous system. Periodontal ligament (PDL) cells were recently reported to express Metabotropic Glutamate Receptors (mGluRs). However, the functions of mGluR signaling in PDL cells or PDL-related cells remain largely unknown. The aim of this study was to investigate the expression and function of mGluRs in PDL-related cells.

Materials and methods: OCCM-30 cells, immortalized murine cementoblasts, were stimulated with l-glutamate or mGluRs antagonists. The cells' proliferative response was evaluated using a colorimetric assay and gene expression was assessed using real-time polymerase chain reaction. The nuclear translocation of cyclin D1 was evaluated by immunohistochemistry.

Results: l-Glutamate promoted the proliferation of OCCM-30 cells, which expressed mGluR1, but not mGluR5. Dihydroxyphenylglycine (DHPG), an agonist of group I mGluRs (mGluR1 and mGluR5), also promoted cell proliferation, and this was inhibited by LY456236, an mGluR1 Antagonist. DHPG increased the expression of cyclin D1, a key regulator of cell proliferation, and its nuclear translocation. DHPG also increased the expression of Bcl2A1, an antiapoptotic oncogene and simultaneously reduced the expression of Bax, a pro-apoptotic marker. Furthermore, the DHPG-induced proliferation of OCCM-30 cells was reduced by pretreatment with SB203580, SP600125, and PD98059, inhibitors of p38, JNK, and ERK1/2, respectively.

Conclusions: These findings indicate that activation of mGluR1 expressed by OCCM-30 cells induces cell proliferation in a manner that is dependent on mitogen-activated protein kinase pathways and that cyclin D1 and Bcl2A1/Bax may be involved. Our results provide useful information for elucidating the mechanisms underlying cementum homeostasis and regeneration.

Keywords

Bcl2A1/Bax; MAP kinases; cementoblast; mGluR1; proliferation; proliferation cementoblast.

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