Cyclic tensile force-upregulated IL6 increases MMP3 expression by human periodontal ligament cells

Tantilertanant, Yanee; Niyompanich, Jitti; Everts, Vincent; Supaphol, Pitt; Pavasant, Prasit; Sanchavanakit, Neeracha

doi:10.1016/j.archoralbio.2019.104495

Cited by 22 publications

(12 citation statements)

References 54 publications

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“…This MMP-3 up-regulation was consistent with that in a previous report by Tantilertanant et al. 20 on tension force-induced IL-6-mediated MMP-3 up-regulation in human PDL cells. However, cells of PDL origin are a mixed population, including fibroblasts, endothelial cells, cementoblasts, osteoblasts, and osteoclasts.…”

Section: Discussionsupporting

confidence: 92%

Orthodontic force regulates metalloproteinase-3 promoter in osteoblasts and transgenic mouse models

Hsu

Chang

Tseng

et al. 2022

Journal of Dental Sciences

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Background/purpose Previously we demonstrated up-regulation of matrix metalloproteinase-3 ( MMP-3 ) in human osteoblasts under compression and in bony specimens of experimental orthodontic tooth movement (OTM). Here, we studied the temporal characteristics of compression stimulation in human and mouse osteoblast cell lines, and generated a transgenic mouse model for assessing the MMP-3 expression during OTM. Materials and methods We investigated MMP-3 expressions in human and murine osteoblasts through RT-PCR and luciferase assay, after compressive force loading. Inhibitors were added to identify the possible mechanisms for signal transduction. A human MMP-3 promoter was isolated, cloned and transfected to generate a transgenic mouse with a green fluorescent protein reporter. OTM was then initiated to observe the location and time course of transcriptional regulation of MMP-3 signals. Results We found changes in the transcription of MMP-3 in response to mechanical force applied to both human and mouse osteoblast cell lines, suggesting that the response is positive across species. Cloned human MMP-3 promoter may cause the response of luciferase to 1% compression. Moreover, p38 inhibitor exerted a down-regulatory effect on MMP-3 promoter expression, although the inhibitory effect didn't reach a significant level. In the transgenic mouse OTM model, we again found increased expression of MMP-3 in response to mechanical force loading around the periodontal ligament. Conclusion Mechanical force can stimulate MMP-3 expression, possibly through the p38 MAPK pathway, with its strongest signal occurring at 24 h. The mechanical responsiveness in MMP-3 promoter regions can be observed in both humans and rodents in vitro and in vivo.

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Section: Discussionsupporting

confidence: 92%

Orthodontic force regulates metalloproteinase-3 promoter in osteoblasts and transgenic mouse models

Hsu

Chang

Tseng

et al. 2022

Journal of Dental Sciences

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“…This process is initiated by an aseptic inflammatory response onsetting early several days after loading. Several in vitro studies demonstrated that CTS activates the production of numerous proinflammatory mediators [25,[46][47][48][49]. Moreover, application of CTS to human PDL cells Fig.…”

Section: Discussionmentioning

confidence: 99%

“…Magnitude is a critical parameter of CTS, which could bring on disparate effects on inflammatory responses, but the pattern of magnitude-dependence was not reported consistently. CTS-modulated production of inflammatory cytokines, both under basal or inflammatory stimulation environment, was observed to increase with the force magnitude [ 48 , 49 , 52 ] or remain no increase until a certain force magnitude level. [ 9 , 28 , 31 ].…”

Section: Discussionmentioning

confidence: 99%

“…Briefly, mechanical stress with specific parameters can exert pro-inflammatory effects in human PDL cells, including up-regulation of IL-6 and IL-8. For example, the application of CTS with 10% elongation and a frequency of 1 Hz yielded an increased the level of IL-6 in primary human PDL cells within the first 2- or 6 h of strain [ 48 ]. Similar observations with an increased IL-6 have been made with the application of static tension [ 57 ], hydrostatic pressure (HP) [ 26 ], or vibration with 30 Hz [ 63 ].…”

Section: Discussionmentioning

confidence: 99%

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Cyclic tensile strain affects the response of human periodontal ligament stromal cells to tumor necrosis factor-α

et al. 2021

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Objectives Orthodontic treatment in adult patients predisposed to mild or severe periodontal disease is challenging for orthodontists. Orthodontic malpractice or hyper-occlusal forces may aggravate periodontitis-induced destruction of periodontal tissues, but the specific mechanism remains unknown. In the present study, the combined effect of mechanical stress and tumor necrosis factor (TNF)-α on the inflammatory response in human periodontal ligament stromal cells (hPDLSCs) was investigated. Materials and methods hPDLSCs from 5 healthy donors were treated with TNF-α and/or subjected to cyclic tensile strain (CTS) of 6% or 12% elongation with 0.1 Hz for 6- and 24 h. The gene expression of interleukin (IL)-6, IL-8 and cell adhesion molecules VCAM and ICAM was analyzed by qPCR. The protein levels of IL-6 and IL-8 in conditioned media was measured by ELISA. The surface expression of VCAM-1 and ICAM-1 was quantified by immunostaining followed by flow cytometry analysis. Results TNF-α-induced IL-6 gene and protein expression was inhibited by CTS, whereas TNF-α-induced IL-8 expression was decreased at mRNA expression level but enhanced at the protein level in a magnitude-dependent manner. CTS downregulated the gene expression of VCAM-1 and ICAM-1 under TNF-α stimulation, but the downregulation of the surface expression analyzed by flow cytometry was observed chiefly for VCAM-1. Conclusions Our findings show that mechanical force differentially regulates TNF-α-induced expression of inflammatory mediators and adhesion molecules at the early stage of force application. The effect of cyclic tensile strain is complex and could be either anti-inflammatory or pro-inflammatory depending on the type of pro-inflammatory mediators and force magnitude. Clinical relevance Orthodontic forces regulate the inflammatory mediators of periodontitis. The underlying mechanism may have significant implications for future strategies of combined periodontal and orthodontic treatment.

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“…However, stretching at magnitude higher than 10 % resulted in no difference between experimental and control [19]. In a same way, tensile cycles are believed to up-regulate the production of metalloproteinase proteins needed in the degradation of old or damaged collagen at low (1.5 %, [155]) or high (10 %, [156,157]) magnitude of stretching. Tensile strain also plays a role in the bone remodeling at the interface between the bone and the PDL.…”

Section: Figure 4 Focused Ionized Beam / Scanning Electronic Microscomentioning

confidence: 97%

Tissue Engineering for Periodontal Ligament Regeneration: Biomechanical Specifications

Gauthier

Jeannin

Attik

et al. 2020

Journal of Biomechanical Engineering

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The periodontal biomechanical environment is very difficult to investigate. By the complex geometry and composition of the periodontal ligament, its mechanical behavior is very dependent on the type of loading (compressive vs. tensile loading; static vs. cyclic loading; uniaxial vs. multiaxial) and the location around the root (cervical, middle, or apical). These different aspects of the periodontal ligament make it difficult to develop a functional biomaterial to treat periodontal attachment due to periodontal diseases. This review aims to describe the structural and biomechanical properties of the periodontal ligament. Particular importance is placed in the close interrelationship that exists between structure and biomechanics: the periodontal ligament structural organization is specific to its biomechanical environment, and its biomechanical properties are specific to its structural arrangement. This balance between structure and biomechanics can be explained by a mechanosensitive periodontal cellular activity. These specifications have to be considered in the further tissue engineering strategies for the development of an efficient biomaterial for periodontal tissues regeneration.

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Cyclic tensile force-upregulated IL6 increases MMP3 expression by human periodontal ligament cells

Cited by 22 publications

References 54 publications

Orthodontic force regulates metalloproteinase-3 promoter in osteoblasts and transgenic mouse models

Orthodontic force regulates metalloproteinase-3 promoter in osteoblasts and transgenic mouse models

Cyclic tensile strain affects the response of human periodontal ligament stromal cells to tumor necrosis factor-α

Tissue Engineering for Periodontal Ligament Regeneration: Biomechanical Specifications

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