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      In Vitro Weight-Loaded Cell Models for Understanding Mechanodependent Molecular Pathways Involved in Orthodontic Tooth Movement: A Systematic Review

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          Abstract

          Cells from the mesenchymal lineage in the dental area, including but not limited to PDL fibroblasts, osteoblasts, and dental stem cells, are exposed to mechanical stress in physiological (e.g., chewing) and nonphysiological/therapeutic (e.g., orthodontic tooth movement) situations. Close and complex interaction of these different cell types results in the physiological and nonphysiological adaptation of these tissues to mechanical stress. Currently, different in vitro loading models are used to investigate the effect of different types of mechanical loading on the stress adaptation of these cell types. We performed a systematic review according to the PRISMA guidelines to identify all studies in the field of dentistry with focus on mechanobiology using in vitro loading models applying uniaxial static compressive force. Only studies reporting on cells from the mesenchymal lineage were considered for inclusion. The results are summarized regarding gene expression in relation to force duration and magnitude, and the most significant signaling pathways they take part in are identified using protein-protein interaction networks.

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          Most cited references51

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          Periodontal ligament cells under mechanical stress induce osteoclastogenesis by receptor activator of nuclear factor kappaB ligand up-regulation via prostaglandin E2 synthesis.

          Previously, we discovered that periodontal ligament (PDL) cells not only support osteoclastogenesis through cell-to-cell contact, but also inhibit the formation of tartrate-resistant acid phosphatase-positive (TRAP+) multinucleated cells by a producing soluble factor(s). Furthermore, PDL cells express both receptor activator of nuclear factor kappaB ligand (RANKL) and osteoprotegerin (OPG) messenger RNA (mRNA). Clinically, "ankylosed teeth," which lack periodontal ligament, cannot be moved with orthodontic tooth treatment. From this, we hypothesized that PDL cells under mechanical stress should play a pivotal role in osteoclast formation during orthodontic tooth movement. This study examined how mechanical stress affects the osteoclastogenesis-supporting activity of PDL cells. PDL cells were compressed continuously and then cocultured with peripheral blood mononuclear cells (PBMCs) for 4 weeks. PDL cells under mechanical stress up-regulated osteoclastogenesis from PBMCs. Furthermore, the expression of RANKL mRNA and protein in PDL cells increased with compressive force in parallel with the change in the number of osteoclasts. In addition, cyclo-oxygenase 2 (COX-2) mRNA expression was induced by compressive force, and indomethacin inhibited the RANKL up-regulation resulting from compressive force. PDL cells under compressive force exhibited significantly increased prostaglandin E2 (PGE2) production in comparison with control PDL cells. Exogenous PGE2 treatment increased RANKL mRNA expression in PDL cells. Interestingly, OPG expression remained constant throughout compressive force or PGE2 treatment. In conclusion, compressive force up-regulated RANKL expression in PDL cells. Furthermore, RANKL up-regulation in mechanically stressed PDL cells was dependent on PGE2.
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            Functional role of mechanosensitive ion channel Piezo1 in human periodontal ligament cells.

            To evaluate the function of Piezo1, an evolutionarily conserved mechanically activated channel, in periodontal ligament (PDL) tissue homeostasis under compressive loading.
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              Levels of RANKL and OPG in gingival crevicular fluid during orthodontic tooth movement and effect of compression force on releases from periodontal ligament cells in vitro.

              To determine the levels of the receptor activator of NFkB ligand (RANKL) and osteoprotegerin (OPG) in the gingival crevicular fluid (GCF) during orthodontic tooth movement. A second objective was to investigate the effect of compression force on RANKL and OPG production from human periodontal ligament (hPDL) cells. Ten adolescent patients were included. GCF was collected at the distal cervical margins of the experimental and control teeth 0, 1, 24, and 168 h after the retracting force was applied. Thisin vitro study was performed to examine the secretion of RANKL and OPG from hPDL cells following a compression force (0, 0.5, 1.0, 2.0, or 3.0 g/cm(2) for 48 h). Enzyme-linked immunosorbent assay (ELISA) kits were used to determine RANKL and OPG levels in the GCF and the conditioned medium. GCF levels of RANKL were significantly higher, and the levels of OPG significantly lower, in the experimental canines than in the control teeth at 24 h, but there were no such significant differences at 0, 1, or 168 h. In vitro study indicated that the compression force significantly increased the secretion of RANKL and decreased that of OPG in hPDL cells in a time- and force magnitude-dependent manner. The compression-stimulated secretion of RANKL increased approximately 16.7-fold and that of OPG decreased 2.9-fold, as compared with the control. The results obtained suggest that the changes of amount of RANKL and OPG may be involved in bone resorption as a response to compression force.
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                Author and article information

                Contributors
                Journal
                Stem Cells Int
                Stem Cells Int
                SCI
                Stem Cells International
                Hindawi
                1687-966X
                1687-9678
                2018
                31 July 2018
                : 2018
                : 3208285
                Affiliations
                1Department of Orthodontics and Dentofacial Orthopedics, University Hospital, LMU Munich, 80336 Munich, Germany
                2Experimental Trauma Surgery, Department of Trauma Surgery, University Regensburg Medical Centre, 93053 Regensburg, Germany
                3Department of Preventive and Pediatric Dentistry, Faculty of Medicine, University of Niš, 18000 Niš, Serbia
                Author notes

                Academic Editor: Andrea Ballini

                Author information
                http://orcid.org/0000-0002-0792-6944
                http://orcid.org/0000-0003-3506-0946
                http://orcid.org/0000-0002-4693-6969
                Article
                10.1155/2018/3208285
                6091372
                30154862
                56684478-9541-4861-9bd9-0bee64eb0b44
                Copyright © 2018 Mila Janjic et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 26 January 2018
                : 9 May 2018
                Funding
                Funded by: Fund for Young Talents of the Republic of Serbia
                Funded by: BAYHOST
                Categories
                Review Article

                Molecular medicine
                Molecular medicine

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