title: Inflammatory environment induces gingival tissue-specific mesenchymal stem cells to differentiate towards a pro-fibrotic phenotype.
abstract: BACKGROUND
  Human gingival tissues are prone to hyperplasia under inflammatory stimuli. We have identified gingival tissue-specific mesenchymal stem cells (GMSCs) and found their functional change being correlated with drug-induced gingival hyperplasia. However, whether these cells exhibit characteristics of pro-fibrotic phenotype under inflammatory condition remains unknown.
  
  
  RESULTS
  GMSCs isolated from human normal gingival tissues (N-GMSC) and inflammatory gingival tissues (I-GMSC) were cultured in vitro, representative cytokines were added to simulate the in vivo inflammatory environment. Under the influence of the inflammatory cytokines, GMSCs exhibited higher rate of proliferation than those under normal condition, while their potential for osteogenic and adipogenic differentiation was suppressed. The expression of matrix metalloproteinases (MMP)-1, MMP-2, IL-1, IL-6, TNF-α and type 1 collagen was significantly higher in I-GMSCs than in N-GMSCs. Furthermore, compared with dental pulp stem cells, GMSCs showed different pattern of gene expression and extracellular matrix formation in inflammatory environment.
  
  
  CONCLUSIONS
  Inflammatory microenvironment induces GMSCs to differentiate towards a pro-fibrotic phenotype, which could underlie the hyperplastic appearance of inflammatory gingiva.
authors.affiliation: Department of Orthodontics, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Li
authors.forename: Na
authors.initials: N
authors.lastname: Liu
authors.forename: Jun
authors.initials: J
authors.lastname: Zhou
authors.forename: Liang
authors.initials: L
authors.lastname: Tang
authors.forename: Bofu
authors.initials: B
authors.lastname: Ding
authors.forename: Yinzhong
authors.initials: Y
authors.lastname: Duan
authors.forename: Yan
authors.initials: Y
authors.lastname: Jin
mesh_terms: D000328:Adult; D002454:Cell Differentiation; D002478:Cells, Cultured; D005260:Female; D005355:Fibrosis; D005881:Gingiva / Q000166:cytology / Q000276:immunology* / Q000473:pathology; D005885:Gingival Hyperplasia / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics / Q000276:immunology; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D010641:Phenotype; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology; D055815:Young Adult
chemical_list: D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha