Compressive force regulates orthodontic tooth movement via activating the
            <scp>NLRP3</scp>
            inflammasome

Han, Yineng; Yang, Qingling; Huang, Yiping; Gao, Pengfei; Jia, Lingfei; Zheng, Yunfei; Li, Weiran

doi:10.1096/fj.202200447rr

Cited by 5 publications

(3 citation statements)

References 49 publications

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“…Consistently, NLRP3 and caspase-1 levels increase on the compression side of PDL tissue under orthodontic forces (Han et al, 2022;Yan et al, 2009). These results suggest a close association between compressive mechanical stimuli and PDLC pyroptosis, potentially leading to subsequent odontoclast formation and inflammatory RR-a previously unexplored phenomenon.…”

Section: Introductionsupporting

confidence: 55%

“…Mechanical force can also exacerbate cellular pyroptosis (Liu et al, 2018), and in PDLCs subjected to cyclic stretch, NLRP3 and GSDMD were activated to induce PDLC pyroptosis and IL‐1β secretion (Zhao et al, 2016; Zhuang et al, 2019). Consistently, NLRP3 and caspase‐1 levels increase on the compression side of PDL tissue under orthodontic forces (Han et al, 2022; Yan et al, 2009). These results suggest a close association between compressive mechanical stimuli and PDLC pyroptosis, potentially leading to subsequent odontoclast formation and inflammatory RR—a previously unexplored phenomenon.…”

Section: Introductionmentioning

confidence: 68%

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NLRP3‐mediated periodontal ligament cell pyroptosis promotes root resorption

Li,

Men,

et al. 2024

J Clinic Periodontology

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AimTo investigate the mechanisms by which periodontal ligament cells (PDLCs) convert biomechanical stimulation into inflammatory microenvironment inducing root resorption (RR).Materials and MethodsRNA sequencing was employed to explore mechanisms in force‐inflammatory signal transduction. Then resorption volume, odontoclastic activity, PDLC pyroptotic ratio and NOD‐like receptor protein 3 (NLRP3)‐mediated pyroptosis pathway activation were analysed under force and pyroptosis inhibition. Further osteoclast formation, macrophage number and transwell polarization demonstrated the effects of PDLC pyroptosis on osteoclastogenesis and M1 polarization.ResultsRNA sequencing revealed that NLRP3‐mediated PDLC pyroptosis induced by Toll‐like receptor 4 (TLR4)/nuclear factor kappa B (NFκB)/NLRP3 pathway may be involved in mechano‐inflammatory signal transduction. PDLC pyroptosis under force and the expression of NLRP3‐mediated pyroptosis pathway in force‐enhanced PDLCs were significantly increased, both in vivo and in vitro. MCC950 administration was sufficient to reduce PDLC pyroptosis and alleviate RR, odontoclast formation and M1 polarization in vivo. Further in vitro exploration showed that MCC950 treatment reduced PDLC force‐promoted pyroptosis and blocked NLRP3‐mediated pyroptosis pathway. Moreover, by treating THP‐1 with force‐pretreated PDLCs or supernatants, NLRP3‐mediated PDLC pyroptotic released products induced osteoclast formation and M1 polarization.ConclusionsNLRP3‐mediated PDLC pyroptosis promotes RR. PDLCs transmit excessive force into inflammation signals through TLR4/NFκB/NLRP3 pathway, inducing PDLC pyroptosis, which directly promotes odontoclast formation and subsequent RR or promotes M1 polarization to indirectly trigger odontoclastogenesis and RR.

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Section: Introductionsupporting

confidence: 55%

Section: Introductionmentioning

confidence: 68%

NLRP3‐mediated periodontal ligament cell pyroptosis promotes root resorption

Li,

Men,

et al. 2024

J Clinic Periodontology

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“…The controversy surrounding the effectiveness of LIPUS in OTM arises from the unclear understanding of its mechanism of action on orthodontic bone remodeling, necessitating further investigation. Osteoclast differentiation serves as the initiating factor for initiating OTM ( Han et al, 2022 ; Xie et al, 2022 ). Therefore, the assessment of the impact of LIPUS on the rate OTM mainly relies on its potential influence on osteoclast differentiation on the pressure side.…”

Section: Introductionmentioning

confidence: 99%

Low-intensity pulsed ultrasound promotes the osteogenesis of mechanical force-treated periodontal ligament cells via Piezo1

Zheng,

Wu,

Wang

et al. 2024

Front. Bioeng. Biotechnol.

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BackgroundLow-intensity pulsed ultrasound (LIPUS) can accelerate tooth movement and preserve tooth and bone integrity during orthodontic treatment. However, the mechanisms by which LIPUS affects tissue remodeling during orthodontic tooth movement (OTM) remain unclear. Periodontal ligament cells (PDLCs) are pivotal in maintaining periodontal tissue equilibrium when subjected to mechanical stimuli. One notable mechano-sensitive ion channel, Piezo1, can modulate cellular function in response to mechanical cues. This study aimed to elucidate the involvement of Piezo1 in the osteogenic response of force-treated PDLCs when stimulated by LIPUS.MethodAfter establishing rat OTM models, LIPUS was used to stimulate rats locally. OTM distance and alveolar bone density were assessed using micro-computed tomography, and histological analyses included hematoxylin and eosin staining, tartrate-resistant acid phosphatase staining and immunohistochemical staining. GsMTx4 and Yoda1 were respectively utilized for Piezo1 functional inhibition and activation experiments in rats. We isolated human PDLCs (hPDLCs) in vitro and evaluated the effects of LIPUS on the osteogenic differentiation of force-treated hPDLCs using real-time quantitative PCR, Western blot, alkaline phosphatase and alizarin red staining. Small interfering RNA and Yoda1 were employed to validate the role of Piezo1 in this process.ResultsLIPUS promoted osteoclast differentiation and accelerated OTM in rats. Furthermore, LIPUS alleviated alveolar bone resorption under pressure and enhanced osteogenesis of force-treated PDLCs both in vivo and in vitro by downregulating Piezo1 expression. Subsequent administration of GsMTx4 in rats and siPIEZO1 transfection in hPDLCs attenuated the inhibitory effect on osteogenic differentiation under pressure, whereas LIPUS efficacy was partially mitigated. Yoda1 treatment inhibited osteogenic differentiation of hPDLCs, resulting in reduced expression of Collagen Ⅰα1 and osteocalcin in the periodontal ligament. However, LIPUS administration was able to counteract these effects.ConclusionThis research unveils that LIPUS promotes the osteogenesis of force-treated PDLCs via downregulating Piezo1.

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Reduced graphene oxide loaded with tetrahedral framework nucleic acids for combating orthodontically induced root resorption

Yuan,

Huang,

Chen

et al. 2024

J Nanobiotechnol

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Root resorption occurs outside the root or within the root canal. Regardless of its region, root resorption is irreversible and in severe cases, may even cause tooth loss. Clinically, the external surface root resorption is usually a side effect of orthodontic tooth movement. However, it is frustrating to note that there are almost no effective treatment strategies for orthodontically induced root resorption (OIRR) due to the complexity and ambiguity of etiology. In the current study, we successfully fabricated a delivery complex, reduced graphene oxide nanosheet loading with tetrahedral framework nucleic acids (tFNAs-rGO) through self-assembly. No significant cytotoxicity or organ-toxicity of the tFNAs-rGO complex was observed in cell counting kit-8 assay (CCK-8) and hematoxylin-eosin (HE) staining. Histological staining such as tartrate-resistant acid phosphatase (TRAP) staining and Micro-CT three-dimensional reconstruction were employed to explore the dynamic changes of root and peri-root tissues in OIRR mice. In vitro, we developed an induction microenvironment to testify the effects of the tFNAs-rGO delivery complex on periodontal ligament cells (PDLCs) and macrophages by quantitative RT-PCR, western blot, and immunofluorescence staining. The data showed the reduced the region of root resorption and downregulated osteoclastic activity in OIRR by the tFNAs-rGO complex treatment. Furthermore, our study demonstrated that the tFNAs-rGO delivery complex enhanced osteogenic differentiation of PDLCs and facilitated M2-phenotype polarization of macrophages to ameliorate OIRR. Collectively, the insight into the nanoscale dual-functional tFNAs-rGO delivery complex regulating the cell populations of PDLCs and macrophages in the root resorption remodeling proposes a promising therapeutic strategy for orthodontically induced root resorption. Supplementary Information The online version contains supplementary material available at 10.1186/s12951-024-02988-2.

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Compressive force regulates orthodontic tooth movement via activating the NLRP3 inflammasome

Cited by 5 publications

References 49 publications

NLRP3‐mediated periodontal ligament cell pyroptosis promotes root resorption

NLRP3‐mediated periodontal ligament cell pyroptosis promotes root resorption

Low-intensity pulsed ultrasound promotes the osteogenesis of mechanical force-treated periodontal ligament cells via Piezo1

Reduced graphene oxide loaded with tetrahedral framework nucleic acids for combating orthodontically induced root resorption

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