Cross-disease transcriptomic screening identifies fibroblast-associated mediators shared across periodontitis and rheumatoid arthritis.

OBJECTIVES

Periodontitis and rheumatoid arthritis (RA) are chronic inflammatory diseases characterized by progressive tissue destruction, and numerous studies have suggested that they are linked. However, the molecular mechanisms underlying this association remain unclear. The aim of this study was to identify molecular pathways beyond classical inflammation and immunity that are commonly dysregulated in periodontitis and RA.

METHODS

We performed in silico screening of publicly available transcriptomic datasets for periodontitis and RA. Next, we performed experimental validation of candidate molecules in an in vitro culture model designed to mimic periodontal tissue under RA-associated conditions.

RESULTS

Comparative analyses of healthy controls identified 540 differentially expressed genes (DEGs) in periodontitis, 4019 DEGs in RA, and 117 commonly upregulated DEGs. Among these, CHI3L2 and MMP3 were selected for further investigation and were found to be prominently expressed in gingival fibroblasts. Quantitative real-time polymerase chain reaction analyses showed that both genes were significantly upregulated by lipopolysaccharide stimulation and by conditioned medium derived from RA synovial cells, with a synergistic enhancement observed when both stimuli were applied simultaneously. Co-culture and wound-healing assays showed that RA synovial cells impaired proliferation and migration of gingival fibroblasts.

CONCLUSIONS

RA-associated pathological factors may influence the responsiveness of periodontal tissue to inflammatory stimuli. Although periodontitis and RA are primarily driven by immune-mediated inflammation, tissue-level molecular expression and sensitivity to stimulus may also be altered, providing complementary insights into shared disease mechanisms and their potential relevance for clinical management.