Hydroxytyrosol Prevents Alveolar Bone Loss in Periodontitis Through Dual Regulation Role in Mitochondrial Function and MAPK Signaling of Bone Cells

Abstract

Background: Reactive oxygen species (ROS) overproduction promotes the alveolar bone loss during the development of periodontitis. Mitochondria are the principal source of ROS. Hydroxytyrosol (HT) is well known for its antioxidant and mitochondrial-protective prosperities. Nonetheless, the impact of HT on periodontitis and its related mechanisms underlying bone cell behavior remains unknown. \n \nMethods: Osteoclasts differentiated from RAW264.7 model and oxidative stress (OS) induced pre-osteoblast MC3T3-E1 cell injury model were treated with and without HT. Cell viability, apoptosis, differentiation, mitochondrial function along with MAPK signaling pathway were investigated. Meanwhile, the effect and related mechanisms of HT on bone loss in mice with periodontitis were also detected. \n \nFindings: HT inhibited osteoclast differentiation and prevented OS induced pre-osteoblast cells injury via regulating mitochondrial function as well as ERK and JNK signaling pathways. Moreover, HT attenuated the alveolar bone loss, increased bone forming activity, inhibited the osteoclasts differentiation and decreased the level of OS in mice with periodontitis. \n \nInterpretation: Our findings, for the first time, revealed a novel function of hydroxytyrosol in bone remodeling of periodontitis, and highlighted its therapeutical potential for the prevention/treatment of periodontitis. \n \nFunding: National Natural Science Foundation of China (81870757, 81870777), Zhejiang Provincial Outstanding Youth Science Foundation (LR21H140002) and Zhejiang Provincial Science and Technology Project for Public Welfare (GF21H140019). \n \nEthical Approval: All animal-related experimental protocols were approved by the Animal Ethics Committee of Wenzhou Medical University (SYXK2019-0019).