牙龈成纤维细胞在牙周炎发病机制中的作用研究进展OA

Periodontitis is a chronic inflammatory disease triggered by periodontal pathogens and mediated by im-mune responses.Traditionally,gingival fibroblasts(GFs)were considered to be primarily responsible for maintaining periodontal matrix homeostasis.However,recent studies reveal that GFs play a significant immunoregulatory role in periodontitis.Through signaling pathways,such as the Toll-like receptor 4(TLR4)pathway,GFs recognize virulence fac-tors from pathogens,such as Porphyromonas gingivalis,and secrete various inflammatory mediators,thus driving extra-cellular matrix degradation and osteoclast differentiation.Simultaneously,GFs modulate immune cells,including neutro-phils and macrophages,amplifying inflammatory responses and fostering a chronic inflammatory microenvironment.Risk factors,such as hyperglycemia and smoking,exacerbate GFs dysfunction via oxidative stress-mediated activation of the nuclear factor kappa B(NF-κB)pathway and other mechanisms,while inflammation and cellular senescence form a vicious cycle.Senescent GFs further aggravate alveolar bone destruction by activating the mechanistic target of the ra-pamycin(mTOR)pathway.Therapeutic strategies targeting GFs,such as suppressing NF-κB signaling or modulating mTOR-mediated senescence,may disrupt the link between inflammation and tissue destruction,showing promising therapeutic potential.Future studies should employ advanced technologies such as spatial multi-omics and single-cell proteomics to elucidate the spatial distribution,functional interactomes,and heterogeneity of GFs subsets,in order to deepen our understanding of their roles in periodontitis progression.This review summarizes the multifaceted mecha-nisms of GFs in periodontitis and explores potential therapeutic strategies targeting GFs,offering novel insights for peri-odontitis prevention and treatment.