The role of extracellular matrix metalloproteinase inducer glycosylation in regulating matrix metalloproteinases in periodontitis

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Background and Objective:

Extracellular matrix metalloproteinase inducer (EMMPRIN) is a transmembrane glycoprotein that may induce activation of matrix metalloproteinases (MMPs) and lead to the destruction of periodontal tissue. The level of EMMPRIN glycosylation might be involved in this process. This study aims to investigate the role of EMMPRIN glycosylation in regulating MMP-2 and MMP-9 during the progression of periodontitis.

Material and Methods:

Gingival tissues were collected from patients with chronic periodontitis and from patients undergoing crown-lengthening procedures (healthy gingival tissue). Tissues were used for immunohistochemistry and double immunofluorescence. A human immortalized oral epithelial cell (HIOEC) line was stably transfected by an N-acetylglucosaminyltransferase-V (GnT-V) RNA interference (RNAi) lentivirus to suppress EMMPRIN glycosylation. Gene silence efficiency was detected by western blot, quantitative real-time PCR and immunofluorescence (IF) staining. An HIOEC/human gingival fibroblast (HGF) co-culture model and an individual culture model were used in this study. After exposure of cells to Porphyromonas gingivalis lipopolysaccharide (Pg. LPS), the expression of EMMPRIN, MMP-2 and MMP-9 were assessed by western blot, quantitative real-time PCR and IF, and the secretion of MMP-2 and MMP-9 were detected by gelatin-degradation assays.


Compared with the periodontally healthy group, patients with periodontitis showed increased expression of EMMPRIN on the gingival epithelial cell membrane. GnT-V, a key regulator of EMMPRIN glycosylation, was co-expressed with EMMPRIN in gingival epithelial cells in patients with periodontitis. Knockdown of GnT-V reduced the level of EMMPRIN glycosylation in HIOECs. Furthermore, in the HIOEC/HGF co-culture model, stimulation with Pg. LPS (10 μg/mL, 4 hours) promoted EMMPRIN glycosylation and increased the activities of MMP-2 and MMP-9, while suppression of EMMPRIN glycosylation by GnT-V knockdown reduced the synthesis and activities of MMP-2 and MMP-9 under Pg. LPS stimulation. Moreover, the gelatin-degradation assay showed that inhibition of EMMPRIN glycosylation suppressed the Pg. LPS-induced degradation of gelatin in the co-culture model.


We conclude that EMMPRIN glycosylation participates in the regulation of MMP-2 and MMP-9 production through mediating the interaction of HIOECs and HGFs. Inhibiting EMMPRIN glycosylation can reduce the activation of MMP-2 and MMP-9 and suppress the degradation of extracellular matrix (ECM) in the HIOEC/HGF co-culture model. Therefore, this study suggests that EMMPRIN glycosylation may affect the host immune-inflammatory response by regulating MMPs in periodontitis.

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