title: Effects of glutamine on proliferation, migration, and differentiation of human dental pulp cells.
abstract: BACKGROUND
  Although glutamine (Gln) is mitogenic in various cell types, little is known about its role in human dental pulp cells (HDPCs). This study investigated the effects of Gln on proliferation, migration, and odontoblastic differentiation of HDPCs and the underlying signal pathway mechanisms.
  
  
  METHODS
  Growth and migration were assessed by cell counting and colorimetric cell migration kits. Differentiation was measured as alkaline phosphatase activity, calcified nodule formation by alizarin red staining, and marker mRNA expression by reverse transcriptase-polymerase chain reaction (RT-PCR). Chemokine expression was also evaluated by RT-PCR. Signal transduction pathways were examined by RT-PCR and Western blot analysis.
  
  
  RESULTS
  Gln dose-dependently increased proliferation, migration, alkaline phosphatase activity, mineralized nodule formation, and odontoblast-marker mRNA of HDPCs. Gln also up-regulated expression of interleukin-6, interleukin-8, MCP-1, MIP-3α, CCL2, CCL20, and CXCL1. Gln increased BMP-2 and BMP-4 mRNA, phosphorylation of Smad 1/5/8, β-catenin, and key proteins of the Wnt signaling pathway. Furthermore, Gln resulted in up-regulation of extracellular signal-regulated kinase, p38, and c-Jun N-terminal kinase. In addition, noggin, DKK1, inhibitors of p38, ERK, and JNK significantly attenuatted Gln-induced growth, migration, and odontoblastic differentiation.
  
  
  CONCLUSIONS
  Collectively, this study demonstrated that Gln promoted growth, migration, and differentiation in HDPCs through the BMP-2, Wnt, and MAPK pathways, leading to improved pulp repair and regeneration.
authors: Department of Conservative Dentistry, School of Dentistry, Kyung Hee University, Seoul, Republic of Korea.
authors: Duck-Su
authors: DS
authors: Kim
authors: Department of Oral Anatomy, School of Dentistry, Kyung Hee University, Seoul, Republic of Korea.
authors: Seong-Suk
authors: SS
authors: Jue
authors: Department of Maxillofacial Tissue Regeneration and Research Center for Tooth and Periodontal Regeneration (MRC), School of Dentistry, Kyung Hee University, Seoul, Republic of Korea.
authors: So-Youn
authors: SY
authors: Lee
authors: Department of Maxillofacial Tissue Regeneration and Research Center for Tooth and Periodontal Regeneration (MRC), School of Dentistry, Kyung Hee University, Seoul, Republic of Korea.
authors: Young-Suk
authors: YS
authors: Kim
authors: Department of Periodontology, School of Dentistry, Kyung Hee University, Seoul, Republic of Korea.
authors: Seung-Yun
authors: SY
authors: Shin
authors: Department of Maxillofacial Tissue Regeneration and Research Center for Tooth and Periodontal Regeneration (MRC), School of Dentistry, Kyung Hee University, Seoul, Republic of Korea. Electronic address: eckim@khu.ac.kr.
authors: Eun-Cheol
authors: EC
authors: Kim
mesh_terms: D000469:Alkaline Phosphatase / Q000032:analysis; D055396:Bone Morphogenetic Protein 2 / Q000032:analysis; D055415:Bone Morphogenetic Protein 4 / Q000032:analysis; D002113:Calcification, Physiologic / Q000187:drug effects; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D054415:Chemokine CCL19 / Q000032:analysis; D018932:Chemokine CCL2 / Q000032:analysis; D054360:Chemokine CXCL1 / Q000032:analysis; D003782:Dental Pulp / Q000166:cytology* / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005973:Glutamine / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D015850:Interleukin-6 / Q000032:analysis; D016209:Interleukin-8 / Q000032:analysis; D020935:MAP Kinase Signaling System / Q000187:drug effects; D009804:Odontoblasts / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D051898:Smad1 Protein / Q000032:analysis; D051902:Smad5 Protein / Q000032:analysis; D051904:Smad8 Protein / Q000032:analysis; D060449:Wnt Signaling Pathway / Q000187:drug effects; D051176:beta Catenin / Q000032:analysis
chemical_list: C525718:BMP2 protein, human; C525809:BMP4 protein, human; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; C515460:CCL19 protein, human; C111835:CCL2 protein, human; C495270:CTNNB1 protein, human; C475829:CXCL1 protein, human; C508606:CXCL8 protein, human; D054415:Chemokine CCL19; D018932:Chemokine CCL2; D054360:Chemokine CXCL1; C508600:IL6 protein, human; D015850:Interleukin-6; D016209:Interleukin-8; C497399:SMAD1 protein, human; C497797:SMAD5 protein, human; C107514:SMAD9 protein, human; D051898:Smad1 Protein; D051902:Smad5 Protein; D051904:Smad8 Protein; D051176:beta Catenin; D005973:Glutamine; D000469:Alkaline Phosphatase
keywords: Differentiation; glutamine; growth; human dental pulp cells; migration