TRIM16 protects human periodontal ligament stem cells from oxidative stress-induced damage via activation of PICOT.

Periodontitis is a chronic inflammatory disease that result in severe loss of supporting structures and substantial tooth loss. Oxidative stress is tightly involved in the progression of periodontitis. Tripartite Motif 16 (TRIM16) has been identified as a novel regulatory protein in response to oxidative and proteotoxic stresses. The present study aimed to investigate the role of TRIM16 in human periodontal ligament stem cells (hPDLSCs) under oxidative stress. First, we found that the expression of TRIM16 decreased after exposure to H2O2. Then TRIM16 overexpression alleviated H2O2-induced oxidative stress by enhancing antioxidant capacity and reducing the amount of intracellular reactive oxygen species (ROS) and reactive nitrogen species (RNS). TRIM16 increased cell viability, inhibited cell apoptosis and the depolarization of the mitochondrial membrane potential in hPDLSCs. Furthermore, TRIM16 attenuated H2O2-induced suppression of osteogenic differentiation. Mechanistically, TRIM16 promoted the activation of protein kinase C (PKC)-interacting cousin of thioredoxin (PICOT), p-Akt and Nrf2, while knockdown of PICOT reversed TRIM16-mediated ROS resistance and decreased the expression of p-Akt and Nrf2. In conclusion, TRIM16 alleviated oxidative damage in hPDLSCs via the activation of PICOT/Akt/Nrf2 pathway, suggesting that TRIM16 could be a promising target to develop effective therapies for periodontitis.