UCLA

Apical periodontitis (AP) occurs as a result of bacterial infection of the root canal and subsequent inflammatory signaling at the periapex. The disease is exacerbated by oral bacterial byproducts, including lipopolysaccharide (LPS), that trigger inflammatory cytokine release and bone destruction. Our laboratory recently demonstrated that expression of KDM3C, a histone lysine demethylase, is induced by LPS exposure and that KDM3C regulates inflammatory cytokine expression. In the current study, we investigated the role of KDM3C in generation of AP in mice after pulp exposure. AP was induced in these mice by exposure of dental pulp of maxillary first molars of KDM3C knockout (KO) and wild-type (WT) mice, and apical lesion development was assessed by uCT analysis, Hematoxylin and Eosin (H&E) staining, and immunohistochemical (IHC) staining. Bone marrow-derived macrophages (BMDM) from WT and KO mice were exposed to LPS to assess the role of KDM3C in the regulation of inflammatory signaling. AP formation

occurred in mice 7 – 21 days post-pulp exposure, and the size of the AP lesion was notably increased in KDM3C KO mice when compared with the WT mice. H&E staining revealed strong infiltration of inflammatory cells to the periapex in KO mice, as well as

enrichment of macrophages when stained with F4/80 marker. Expression of inflammatory cytokines, e.g., IL-6, was significantly reduced in BMDM cultured from KDM3C KO mice. These findings indicate that KDM3C plays a critical role in immune response to oral bacterial infection in the root canal, and that loss of KDM3C compromises the inflammatory response and exacerbates development of AP.