Search Results (9)

Orthodontic tooth movement (OTM) is accompanied by sterile inflammation, a necessary biological process that facilitates tooth displacement but also contributes to adverse effects, including hyalinization and orthodontically induced external apical root resorption (OEARR). Despite advancements in orthodontic therapies, the inflammatory response—regulated by dynamic interactions between tissue-specific cells and their molecular mediators—remains a critical factor influencing treatment outcomes. This review summarizes the current understanding of the cellular and molecular mechanisms underlying OTM, with a focus on how these insights can support the development of targeted therapeutic strategies. These include cell- and molecule-based therapies, biomaterial-mediated delivery systems, and applications of artificial intelligence (AI). Notably, AI offers promising opportunities for modeling and simulating biological responses, enabling the optimization of individualized treatment planning. We further discuss current clinical practices and highlight emerging experimental findings, with an emphasis on unresolved research questions pivotal to improving therapeutic efficacy and reducing complications such as OEARR. This comprehensive overview aims to inform future directions in orthodontics by integrating mechanistic knowledge with technological innovation. Full article

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. Full article

Excessive orthodontic force can induce inflammatory tooth root resorption due to sustained high stresses within the periodontal ligament (PDL). This study aimed to analyze the PDL pressures during upper incisor retraction using the en masse method with TISAD. The finite element method (FEM) ensured consistent conditions across cases. The models included bone geometry, adjacent teeth, PDL, and orthodontic hardware, analyzed with LS-Dyna. The pressure ranged from 0.37 to 2.5 kPa across the dental arch, with the central incisors bearing 55% of the load. The pressure distribution remained consistent regardless of the force or hook height. The critical pressure (4.7 kPa) was exceeded at 600–650 g force, with notable pressure (3.88 kPa) on the palatal root wall of the right central incisor. Utilizing 0.017 × 0.025 SS archwires in MBT 0.018 brackets provided good torque control and reduced the root resorption risk when forces of 180–200 g per side were applied, maintaining light to moderate stress. Triple forces may initiate resorption, highlighting the importance of nonlinear finite element analysis (FEA) for accurate oral cavity simulations. Full article

The Robot Orthodontic Measurement and Simulation System (ROSS) is a novel biomechanical, dynamic, self-regulating setup for the simulation of tooth movement. The intrusion of the front teeth with forces greater than 0.5 N poses a risk for orthodontic-induced inflammatory root resorption (OIIRR). The aim was to investigate forces and moments during simulated tooth intrusion using ROSS. Five specimens of sixteen unmodified NiTi archwires and seven NiTi archwires with intrusion steps from different manufacturers (Forestadent, Ormco, Dentsply Sirona) with a 0.012″/0.014″/0.016″ wire dimension were tested. Overall, a higher wire dimension correlated with greater intrusive forces F_z (0.012″: 0.561–0.690 N; 0.014″: 0.996–1.321 N; 0.016″: 1.44–2.254 N) and protruding moments M_x (0.012″: −2.65 to −3.922 Nmm; 0.014″: −4.753 to −7.384 Nmm; 0.016″: −5.556 to −11.466 Nmm) during the simulated intrusion of a 1.6 mm-extruded upper incisor. However, the ‘intrusion efficiency’ parameter was greater for smaller wire dimensions. Modification with intrusion steps led to an overcompensation of the intrusion distance; however, it led to a severe increase in F_z and M_x, e.g., the Sentalloy 0.016″ medium (Dentsply Sirona) exerted 2.891 N and −19.437 Nmm. To reduce the risk for OIIRR, 0.014″ NiTi archwires can be applied for initial aligning (without vertical challenges), and intrusion steps for the vertical levelling of extruded teeth should be bent in the initial archwire, i.e., 0.012″ NiTi. Full article

Orthodontically induced inflammatory root resorption (OIIRR) is considered an undesired and inevitable complication induced by orthodontic forces. This inflammatory mechanism is regulated by immune cells that precede orthodontic tooth movement (OTM) and can influence the severity of OIIRR. The process of OIIRR is based on an immune response. On some occasions, the immune system attacks the dentition by inflammatory processes during orthodontic treatment. Studies on the involvement of the PD-1/PD-L1 immune checkpoint have demonstrated its role in evading immune responses, aiming to identify possible novel therapeutic approaches for periodontitis. In the field of orthodontics, the important question arises of whether PD-L1 has a role in the development of OIIRR to amplify the amount of resorption. We hypothesize that blocking of the PD-L1 immune checkpoint could be a suitable procedure to reduce the process of OIIRR during orthodontic tooth movement. This review attempts to shed light on the regulation of immune mechanisms and inflammatory responses that could influence the pathogenesis of OIIRR and to acquire knowledge about the role of PD-L1 in the immunomodulation involved in OIIRR. Possible clinical outcomes will be discussed in relation to PD-L1 expression and immunologic changes throughout the resorption process. Full article

In animal models, the administration of ciliary neurotrophic factor (CNTF) was demonstrated to reduce bone mass and to participate in bone remodeling. Cementoblasts, a cell type embedded in the cementum, are the main cells to produce and mineralize the extracellular matrix. The effect of CNTF on cementoblasts has not yet been addressed. Thus, the goal of this in vitro study was to investigate possible influences of exogenous CNTF on cementogenesis, as well as autophagy regulation and subsequent mechanisms in cementoblasts. Cementoblasts (OCCM-30) were stimulated with exogenous CNTF. Alizarin Red staining was performed to analyze the functional differentiation (mineralization) of OCCM-30 cells. The release of OPG was quantified by ELISA. The expression of cementogenesis markers (RUNX-2, OCN, BMP-7, BSP, and SPON-2) was evaluated by RT-qPCR. Western blotting (WB) was performed for the protein expression of STAT3, COX-2, SHP-2, cPLAα, cPLAβ; ERK1/2, P38, and JNK. The autophagic flux was assessed using WB and RT-qPCR analysis of LC3A/B, Beclin-1, and Atg-5, and the autophagosome was investigated by immunofluorescence staining (IF). The ERK1/2 (FR180204) or STAT3 (sc-202818) antagonist was added, and the cellular response was analyzed using flow cytometry. Exogenous CNTF significantly attenuated mineralized nodule formation, impaired OPG release, and downregulated the mRNA levels of RUNX-2, OCN, BMP-7, and BSP. Moreover, CNTF induced the phosphorylation of STAT3 and activated a transient activation of SHP-2, cPLAβ, ERK1/2, P38, and JNK protein. CNTF also induced autophagosome formation and promoted autophagy-associated gene and protein expressions. Additionally, the inhibition of ERK1/2 or STAT3 reversed a CNTF-induced mineralization impairment and had regulatory effects on CNTF-induced autophagosome formation. Our data revealed that CNTF acts as a potent inhibitor of cementogenesis, and it can trigger autophagy, in part by ERK1/2 and STAT3 commitment in the cementoblasts. Thus, it may play an important role in inducing or facilitating inflammatory root resorption during orthodontic tooth movement. Full article

Recent studies have revealed that hypoxia alters the PD-L1 expression in periodontal cells. HIF-1α is a key regulator for PD-L1. As hypoxia presents a hallmark of an orthodontically induced microenvironment, hypoxic stimulation of PD-L1 expression may play vital roles in immunorthodontics and orthodontically induced inflammatory root resorption (OIIRR). This study aims to investigate the hypoxic regulation of PD-L1 in cementoblasts, and its interaction with hypoxia-induced HIF-1α expression. The cementoblast (OCCM-30) cells (M. Somerman, NIH, NIDCR, Bethesda, Maryland) were cultured in the presence and absence of cobalt (II) chloride (CoCl₂). Protein expression of PD-L1 and HIF-1α as well as their gene expression were evaluated by Western blotting and RT-qPCR. Immunofluorescence was applied to visualize the localization of the proteins within cells. The HIF-1α inhibitor (HY-111387, MedChemExpress) was added, and CRISPR/Cas9 plasmid targeting HIF-1α was transferred for further investigation by flow cytometry analysis. Under hypoxic conditions, cementoblasts undergo an up-regulation of PD-L1 expression at protein and mRNA levels. Silencing of HIF-1α using CRISPR/Cas9 indicated a major positive correlation with HIF-1α in regulating PD-L1 expression. Taken together, these findings show the influence of hypoxia on PD-L1 expression is modulated in a HIF-1α dependent manner. The HIF-1α/PD-L1 pathway may play a role in the immune response of cementoblasts. Thus, combined HIF-1α/PD-L1 inhibition could be of possible therapeutic relevance for OIIRR prevention. Full article

The aim of this paper is to provide a review on the role of inflammation in orthodontically induced inflammatory root resorption (OIIRR) and accelerating orthodontic tooth movement (AOTM) in orthodontic treatment. Orthodontic tooth movement (OTM) is stimulated by remodeling of the periodontal ligament (PDL) and alveolar bone. These remodeling activities and tooth displacement are involved in the occurrence of an inflammatory process in the periodontium, in response to orthodontic forces. Inflammatory mediators such as prostaglandins (PGs), interleukins (Ils; IL-1, -6, -17), the tumor necrosis factor (TNF)-α superfamily, and receptor activator of nuclear factor (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) are increased in the PDL during OTM. OIIRR is one of the accidental symptoms, and inflammatory mediators have been detected in resorbed roots, PDL, and alveolar bone exposed to heavy orthodontic force. Therefore, these inflammatory mediators are involved with the occurrence of OIIRR during orthodontic tooth movement. On the contrary, regional accelerating phenomenon (RAP) occurs after fractures and surgery such as osteotomies or bone grafting, and bone healing is accelerated by increasing osteoclasts and osteoblasts. Recently, tooth movement after surgical procedures such as corticotomy, corticision, piezocision, and micro-osteoperforation might be accelerated by RAP, which increases the bone metabolism. Therefore, inflammation may be involved in accelerated OTM (AOTM). The knowledge of inflammation during orthodontic treatment could be used in preventing OIIRR and AOTM. Full article

Many patients regularly take histamine receptor antagonists, such as cetirizine, to prevent allergic reactions, but these antiallergic drugs may have inadvertent effects on orthodontic treatment. In previous studies, histamine has been shown to modulate the sterile inflammatory reaction underlying orthodontic tooth movement. Pertinent effects of histamine antagonization via cetirizine during orthodontic treatment, however, have not been adequately investigated. We thus treated male Fischer344 rats either with tap water (control group) or cetirizine by daily oral gavage corresponding to the clinically used human dosage adjusted to the rat metabolism (0.87 mg/kg) or to a previously published high dosage of cetirizine (3 mg/kg). Experimental anterior movement of the first upper left molar was induced by insertion of a nickel-titanium (NiTi) coil spring (0.25 N) between the molar and the upper incisors. Cone-beam computed tomography (CBCT), micro-computed tomography (µCT) images, as well as histological hematoxylin-eosin (HE), and tartrate-resistant acid phosphatase (TRAP) stainings were used to assess the extent of tooth movement, cranial growth, periodontal bone loss, root resorptions, and osteoclast activity in the periodontal ligament. Both investigated cetirizine dosages had no impact on the weight gain of the animals and, thus, animal welfare. Neither the extent of tooth movement, nor cranial growth, nor root resorption, nor periodontal bone loss were significantly influenced by the cetirizine dosages investigated. We, thus, conclude that histamine receptor antagonist cetirizine can be used during orthodontic treatment to prevent allergic reactions without clinically relevant side effects on orthodontic tooth movement. Full article