Matrix Metalloproteinase-1 of Gingival Fibroblasts Influenced by Advanced Glycation End Products (AGEs) and Their Association With Receptor for AGEs and Nuclear Factor-kappa B in Gingival Connective Tissue

Background: The effect of advanced glycation end products (AGEs) on gingival inflammation has not been fully elucidated. This study aims to investigate the hypothesis that AGEs may enhance the expression of matrix metalloproteinase-1 (MMP-1) of human gingival fibroblasts (HGFs) and to explore whether the signal pathway receptor for AGE (RAGE)/nuclear factor-kappa B (NF-kappa B) are involved in the expression of MMP-1 in HGFs. Methods: Cultured HGFs from 12 healthy gingival human tissue samples were coincubated with AGEs for the detection of MMP-1 protein and mRNA. Thirty-six gingival samples were collected and treated for the determination of RAGE, NF-kappa B, and MMP-1 mRNA level in gingival connective tissues from the participants with chronic periodontitis, diabetes-associated periodontitis, and healthy controls. Enzyme-linked immunosorbent assay and real-time fluorescence reverse transcription-polymerase chain reaction were used for the measurement of protein and mRNA level, respectively. In addition, clinical periodontal parameters were also checked. Results: AGEs strongly induced MMP-1 mRNA and protein expression in HGFs and in a time- and concentration-dependent manner (P<0.05). In gingival connective tissue, the level of both RAGE mRNA and NF-kappa B mRNA were higher in patients with periodontitis than in healthy controls (P<0.05). There was significant correlation between the level of RAGE mRNA and NF-kappa B mRNA (R-2 = 0.90, P<0.05). Conclusions: Accumulation of AGEs may upregulate the expression of MMP-1 by HGFs, which may play a role in the development of diabetes-associated periodontitis, and RAGE/NF-kappa B pathway may be involved in metabolism of MMP-1 in HGFs. J Periodontol 2012;83:119-126.