OBJECTIVE: This review aims to provide an overview of the role of microorganisms in the onset and progression of periapical diseases, particularly regarding their effects on bone homeostasis. DESIGN: The search for this narrative review was conducted in PubMed, Web of Science and Google Scholar using relevant keywords, including checking reference lists of journal articles by hand searching. RESULTS: Microorganisms directly promote osteoclasts through pathways such as nuclear factor-kappaB (NF-kappaB) and extracellular regulated protein kinases (ERK), while inhibiting osteoblasts function by interfering with the wingless-related integration site (Wnt)/beta-catenin pathway in the periapical area. Moreover, microorganisms indirectly regulate periapical bone homeostasis by inducing programmed cell death and modulating the immune microenvironment through the activation of innate immunity via pattern-recognition receptors (PRRs) and subsequent cascades of responses. Among these microorganisms, Enterococcus faecalis, Porphyromonas gingivalis and Fusobacterium nucleatum play significant roles. CONCLUSION: Microorganisms regulate pathways such as NF-kB and Wnt/beta-catenin, as well as programmed cell death and the immune microenvironment in the periapical area, thereby disrupting bone homeostasis.
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