UCLA

Aging is associated with a decline in innate and adaptive immune functions resulting in a weakened immune response against infection. Clinically, this decline in immune function leads to age-associated pathologies, including atherosclerosis, type II diabetes, dementia, obesity, and cancer systemically and prevalence of periapical bone loss the prevalence and severity of periodontitis orally. Previously, our lab identified an epigenetic marker KDM3C as a novel regulator of inflammatory signaling. In addition, we demonstrated that KDM3C regulate inflammatory signaling against oral bacterial infection through suppression of NK-κB signaling in macrophage (MΦ). In addition, our preliminary results showed KDM3C expression was inhibited in the aged mice compared to a younger cohort; thus, we hypothesize KDM3C is a key regulator for macrophage polarization during aging. In this project, we found that 1) old (18-20mo) mice had increase in apical bone loss and alveolar bone loss compared to young (2mo) mice following pulp exposure model (PE) and Ligature induced periodontitis model (LIP) respectively; 2) Kdm3c-/- mice revealed increased periapical bone loss compared to the Kdm3c+/+ mice upon PE. Similarly, Kdm3c-/- mice developed increased alveolar bone loss with ligature-induced periodontitis (LIP). 3) KDM3C deletion in mice resulted in increase in inflammatory cytokines levels in liver and spleen. Additionally, we characterize the KDM3C role in macrophage polarization. Here we found that, 1) Anti-inflammatory MΦ (M2) markers were significantly decreased in bone-marrow derived macrophages (BMDM) and in gingival tissue. 2) Histological staining of CD206 expression, a surface marker for M2, showed significant decrease in the positive staining of CD206 in Kdm3c-/- following LIP.