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



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.



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.



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.
a Department of Periodontology and Endodontology , Tohoku University Graduate School of Dentistry , Sendai , Japan.|b Liaison Center for Innovative Dentistry , Graduate School of Dentistry, Tohoku University , Sendai , Japan.
Sousuke
S
Kanaya
a Department of Periodontology and Endodontology , Tohoku University Graduate School of Dentistry , Sendai , Japan.
Hidehiro
H
Komatsu
a Department of Periodontology and Endodontology , Tohoku University Graduate School of Dentistry , Sendai , Japan.
Hidetoshi
H
Shimauchi
a Department of Periodontology and Endodontology , Tohoku University Graduate School of Dentistry , Sendai , Japan.
Eiji
E
Nemoto
D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D003739:Dental Cementum / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology*; D005973:Glutamine / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000494:pharmacology; D051379:Mice; D015778:Minor Histocompatibility Antigens / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D021381:Protein Transport / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*
C096816:BCL2-related protein A1; D015778:Minor Histocompatibility Antigens; D047428:Protein Kinase Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1; D005973:Glutamine; D019938:Cyclin D1; D008734:Methoxyhydroxyphenylglycol; C010117:3,4-dihydroxyphenylglycol
Bcl2A1/Bax; MAP kinases; cementoblast; mGluR1; proliferation; proliferation cementoblast