The Potential Regulatory Role of Ferroptosis in Orthodontically Induced Inflammatory Root Resorption

Abstract

People, in increasing numbers, are seeking orthodontic treatment to correct malocclusion, while some of them are suffering from orthodontically induced inflammatory root resorption (OIIRR). Recent evidence suggests that the immune-inflammatory response occurring during bone remodeling may be responsible for OIIRR. Ferroptosis, a new type of programmed cell death (PCD), has been found to have a close interrelation with inflammation during disease progression. While ferroptosis has been extensively studied in bone-related diseases, its role in OIIRR is poorly understood. Considering that the tooth root shares a lot of similar characteristics with bone, it is reasonable to hypothesize that ferroptosis contributes to the development of OIIRR. Nevertheless, direct evidence supporting this theory is currently lacking. In this review, we introduced ferroptosis and elucidated the mechanisms underlying orthodontic tooth movement (OTM) and OIIRR, with a special focus on the pivotal role inflammation plays in these processes. Additionally, we covered recent research exploring the connections between inflammation and ferroptosis. Lastly, we emphasized the important regulatory function of ferroptosis in bone homeostasis. Further investigations are required to clarify the modulation mechanisms of ferroptosis in OIIRR and to develop novel and potential therapeutic strategies for the management of OIIRR.

Keywords: ferroptosis; inflammation; orthodontic tooth movement; orthodontically induced inflammatory root resorption.

Figure 1

Orthodontic force-induced inflammation may cause root resorption by inducing ferroptosis. The inflammation reactions commence immediately after orthodontic force is applied to the teeth. Inflammatory cytokines, including TNF-α and IL-1β secreted by immune cells, can cause lipid ROS accumulation through stat3 or p53, ultimately inducing ferroptosis. In addition, the NLRP3 inflammasome can trigger the release of IL-1β to induce ferroptosis. Iron and lipid peroxidation can also induce ferroptosis. Ferroptosis of different types of bone cells can result in alveolar bone remodeling, resulting in tooth resorption. Black arrows represent promotion, and red arrows represent the progress of OIIRR.

Figure 2

The signaling pathways that trigger ferroptosis in different kinds of bone cells. Bone cells including osteoblasts, osteoclasts, bone marrow mesenchymal stem cells (BMSCs), and osteocytes can undergo ferroptosis through modulating different signaling pathways. Up arrows represent upregulation (↑), and down arrows represent downregulation (↓).