Role of noncoding RNAs in orthodontic tooth movement: new insights into periodontium remodeling

Abstract

Orthodontic tooth movement (OTM) is biologically based on the spatiotemporal remodeling process in periodontium, the mechanisms of which remain obscure. Noncoding RNAs (ncRNAs), especially microRNAs and long noncoding RNAs, play a pivotal role in maintaining periodontal homeostasis at the transcriptional, post-transcriptional, and epigenetic levels. Under force stimuli, mechanosensitive ncRNAs with altered expression levels transduce mechanical load to modulate intracellular genes. These ncRNAs regulate the biomechanical responses of periodontium in the catabolic, anabolic, and coupling phases throughout OTM. To achieve this, down or upregulated ncRNAs actively participate in cell proliferation, differentiation, autophagy, inflammatory, immune, and neurovascular responses. This review highlights the regulatory mechanism of fine-tuning ncRNAs in periodontium remodeling during OTM, laying the foundation for safe, precise, and personalized orthodontic treatment.

Keywords: Noncoding RNA; Orthodontic tooth movement; Orthodontic treatment; Periodontium remodeling.

Fig. 1

Discovery and characterization of ncRNAs’ functions and mechanisms in OTM. Studies of in vitro force stimulation, mouse or rat OTM models, and samples from orthodontic patients are included in this review. First, comparisons of transcripts from RNA sequencing help identify differentially expressed ncRNAs. Subsequent analyses allow in-depth functional elucidation of ncRNA candidates, which contribute to the biomechanical responses of periodontium by generating phenotypic changes during OTM. Mechanistically, miRNAs regulate gene expression primarily by targeting mRNA, while lncRNAs function at epigenetic, transcriptional, and post-transcriptional levels. Specially, ncRNAs can modulate function of neighbor cells through packaging into extracellular vesicles. In parentheses are some representative examples

Fig. 2

Schematic diagram of ncRNAs regulating periodontium remodeling during OTM. PDL, located between alveolar bone and cementum, is a fibrous connective tissue with neurovascularity and heterogeneous cell groups. A ncRNAs contribute to sensing and transducing mechanical forces in osteocytes and PDLCs. B In the catabolic phase, ncRNAs are involved in osteoclast-mediated bone resorption and PDLC-mediated PDL degradation. C In the subsequent anabolic stage, ncRNAs regulate the function of osteoblasts and PDL synthesis. D ncRNAs are responsible for coordinating delicate communication via cytokines or intercellular contact

Fig. 3

ncRNAs actively participate in cell proliferation, differentiation, autophagy, inflammatory, immune, and neurovascular responses during OTM

Fig. 4

Mechanosensitive ncRNAs regulate the early differentiation of osteoclasts and their functions

Fig. 5

Mechanosensitive ncRNAs regulate osteogenesis through different signals

Fig. 6

ncRNA-based clinical implications in OTM. Efficient delivery of ncRNAs could be used to explore orthodontic optimal forces, improve clinical outcomes, and prevent complications for achieving desired OTM with minimal side effects