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Inflammatory environment induces gingival tissue‐specific mesenchymal stem cells to differentiate towards a pro‐fibrotic phenotype
Authors:Na Liu  Jun Zhou  Liang Tang  Bofu Ding  Yinzhong Duan  Yan Jin
Institution:1. Department of Stomatology, Chinese PLA General Hospital and Medical School of Chinese PLA, Beijing100853, China;2. Department of Oral Histology and Pathology, School of Stomatology, Fourth Military Medical University, Xi’an, Shaanxi 710032, China;3. Research and Development Center for Tissue Engineering, Fourth Military Medical University, Xi’an, Shaanxi 710032, China;4. Department of Operative Dentistry and Endodontics, School of Stomatology, Fourth Military Medical University, Xi’an, Shaanxi 710032, China;5. Department of Orthodontics, School of Stomatology, Fourth Military Medical University, Xi’an, Shaanxi 710032, China
Abstract:

Background Information

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.
Keywords:Extracellular matrix  Gingival mesenchymal stem cells  Inflammatory gingival hyperplasia  Matrix metalloproteinases  TIMPs
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