{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T08:57:42Z","timestamp":1788598662553,"version":"build-2803163510"},"reference-count":45,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,6,23]],"date-time":"2021-06-23T00:00:00Z","timestamp":1624406400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Human Periodontal Ligament Fibroblasts (hPDLF), as part of the periodontal apparatus, modulate inflammation, regeneration and bone remodeling. Interferences are clinically manifested as attachment loss, tooth loosening and root resorption. During orthodontic tooth movement (OTM), remodeling and adaptation of the periodontium is required in order to enable tooth movement. hPDLF involvement in the early phase-OTM compression side was investigated for a 72-h period through a well-studied in vitro model. Changes in the morphology, cell proliferation and cell death were analyzed. Specific markers of the cell cycle were investigated by RT-qPCR and Western blot. The study showed that the morphology of hPDLF changes towards more unstructured, unsorted filaments under mechanical compression. The total cell numbers were significantly reduced with a higher cell death rate over the whole observation period. hPDLF started to recover to pretreatment conditions after 48 h. Furthermore, key molecules involved in the cell cycle were significantly reduced under compressive force at the gene expression and protein levels. These findings revealed important information for a better understanding of the preservation and remodeling processes within the periodontium through Periodontal Ligament Fibroblasts during orthodontic tooth movement. OTM initially decelerates the hPDLF cell cycle and proliferation. After adapting to environmental changes, human Periodontal Ligament Fibroblasts can regain homeostasis of the periodontium, affecting its reorganization.<\/jats:p>","DOI":"10.3390\/biom11070932","type":"journal-article","created":{"date-parts":[[2021,6,23]],"date-time":"2021-06-23T11:28:41Z","timestamp":1624447721000},"page":"932","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["In Vitro Compression Model for Orthodontic Tooth Movement Modulates Human Periodontal Ligament Fibroblast Proliferation, Apoptosis and Cell Cycle"],"prefix":"10.3390","volume":"11","author":[{"given":"Julia","family":"Brockhaus","sequence":"first","affiliation":[{"name":"Department of Orthodontics, Dental Clinic, University Hospital RWTH Aachen, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rogerio B.","family":"Craveiro","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, Dental Clinic, University Hospital RWTH Aachen, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irma","family":"Azraq","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, Dental Clinic, University Hospital RWTH Aachen, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Niederau","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, Dental Clinic, University Hospital RWTH Aachen, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2265-3726","authenticated-orcid":false,"given":"Sarah K.","family":"Schr\u00f6der","sequence":"additional","affiliation":[{"name":"Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry, University Hospital RWTH Aachen, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3888-0931","authenticated-orcid":false,"given":"Ralf","family":"Weiskirchen","sequence":"additional","affiliation":[{"name":"Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry, University Hospital RWTH Aachen, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joachim","family":"Jankowski","sequence":"additional","affiliation":[{"name":"Institute for Molecular Cardiovascular Research, University Hospital RWTH Aachen, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Wolf","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, Dental Clinic, University Hospital RWTH Aachen, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1111\/j.1600-0757.2005.00141.x","article-title":"Structure of periodontal tissues in health and disease","volume":"40","author":"Nanci","year":"2006","journal-title":"Periodontology 2000"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"5238","DOI":"10.1016\/j.biomaterials.2007.08.031","article-title":"The tooth attachment mechanism defined by structure, chemical composition and mechanical properties of collagen fibers in the periodontium","volume":"28","author":"Ho","year":"2007","journal-title":"Biomaterials"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.jdsr.2016.04.002","article-title":"Histology of human cementum: Its structure, function, and development","volume":"52","author":"Yamamoto","year":"2016","journal-title":"Jpn. Dent. Sci. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1016\/j.ajodo.2019.10.017","article-title":"External apical root resorption and vectors of orthodontic tooth movement","volume":"158","author":"Linkous","year":"2020","journal-title":"Am. J. Orthod. Dentofac. Orthop."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1016\/j.ajodo.2007.06.012","article-title":"Identification of orthodontic patients at risk of severe apical root resorption","volume":"135","author":"Doppel","year":"2009","journal-title":"Am. J. Orthod. Dentofac. Orthop."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"672","DOI":"10.2319\/102716-774.1","article-title":"Peridental bone changes after orthodontic tooth movement with fixed appliances: A cone-beam computed tomographic study","volume":"87","author":"Mah","year":"2017","journal-title":"Angle Orthod."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1093\/ejo\/cjl001","article-title":"The tissue, cellular, and molecular regulation of orthodontic tooth movement: 100 Years after Carl Sandstedt","volume":"28","author":"Meikle","year":"2006","journal-title":"Eur. J. Orthod."},{"key":"ref_8","first-page":"151","article-title":"Biological reaction of alveolar bone to orthodontic tooth movement","volume":"69","author":"Melsen","year":"1999","journal-title":"Angle Orthod."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"469.e1","DOI":"10.1016\/j.ajodo.2005.10.007","article-title":"Cellular, molecular, and tissue-level reactions to orthodontic force","volume":"129","author":"Krishnan","year":"2006","journal-title":"Am. J. Orthod. Dentofac. Orthop."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1111\/j.1601-0825.1995.tb00193.x","article-title":"Origins and functions of cells essential for periodontal repair: The role of fibroblasts in tissue homeostasis","volume":"1","author":"McCulloch","year":"1995","journal-title":"Oral Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1007\/s00056-012-0104-1","article-title":"Gene analysis of signal transduction factors and transcription factors in periodontal ligament cells following application of dynamic strain","volume":"73","author":"Deschner","year":"2012","journal-title":"J. Orofac. Orthop."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Ullrich, N., Schr\u00f6der, A., Jantsch, J., Spanier, G., Proff, P., and Kirschneck, C. (2019). The role of mechanotransduction versus hypoxia during simulated orthodontic compressive strain\u2014an in vitro study of human periodontal ligament fibroblasts. Int. J. Oral Sci., 11.","DOI":"10.1038\/s41368-019-0066-x"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"10409","DOI":"10.1096\/fj.201900484R","article-title":"Role of intracellular Ca2+\u2013based mechanotransduction of human periodontal ligament fibroblasts","volume":"33","author":"Hlaing","year":"2019","journal-title":"FASEB J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1016\/j.ajodo.2012.05.012","article-title":"Kinetics of interleukin-6 and chemokine ligands 2 and 3 expression of periodontal tissues during orthodontic tooth movement","volume":"142","author":"Madureira","year":"2012","journal-title":"Am. J. Orthod. Dentofac. Orthop."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Yamaguchi, M., and Fukasawa, S. (2021). Is inflammation a friend or foe for orthodontic treatment?: Inflammation in orthodontically induced inflammatory root resorption and accelerating tooth movement. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22052388"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1007\/s00056-018-0145-1","article-title":"Expression kinetics of human periodontal ligament fibroblasts in the early phases of orthodontic tooth movement","volume":"79","author":"Bauer","year":"2018","journal-title":"J. Orofac. Orthop."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/s10266-015-0206-5","article-title":"Biomechanical force induces the growth factor production in human periodontal ligament-derived cells","volume":"104","author":"Ichioka","year":"2016","journal-title":"Odontology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1007\/s10266-020-00569-x","article-title":"Morpho-functional effects of different universal dental adhesives on human gingival fibroblasts: An in vitro study","volume":"109","author":"Pagano","year":"2021","journal-title":"Odontology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"43","DOI":"10.12968\/denu.2006.33.1.43","article-title":"Limiting factors in orthodontic treatment: 1. Factors related to patient, operator and orthodontic appliances","volume":"33","author":"Shah","year":"2006","journal-title":"Dent. Update"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1302\/2046-3758.81.BJR-2018-0060.R1","article-title":"Effects of mechanical forces on osteogenesis and osteoclastogenesis in human periodontal ligament fibroblasts","volume":"8","author":"Li","year":"2019","journal-title":"Bone Jt. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1359\/jbmr.2002.17.2.210","article-title":"Periodontal ligament cells under mechanical stress induce osteoclastogenesis by receptor activator of nuclear factor \u03baB ligand up-regulation via prostaglandin E2 synthesis","volume":"17","author":"Kanzaki","year":"2002","journal-title":"J. Bone Miner. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"348","DOI":"10.20892\/j.issn.2095-3941.2017.0033","article-title":"Cell cycle regulation and anticancer drug discovery","volume":"14","author":"Jingwen","year":"2017","journal-title":"Cancer Biol. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3208285","DOI":"10.1155\/2018\/3208285","article-title":"In Vitro Weight-Loaded Cell Models for Understanding Mechanodependent Molecular Pathways Involved in Orthodontic Tooth Movement: A Systematic Review","volume":"2018","author":"Janjic","year":"2018","journal-title":"Stem Cells Int."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"10893","DOI":"10.1038\/s41598-020-67449-w","article-title":"Selection and validation of reference genes by RT-qPCR for murine cementoblasts in mechanical loading experiments simulating orthodontic forces in vitro","volume":"10","author":"Niederau","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_25","first-page":"16","article-title":"Establishment and characterization of a human prostatic carcinoma cell line (PC-3)","volume":"17","author":"Kaighn","year":"1979","journal-title":"Investig. Urol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Schr\u00f6der, S.K., Asimakopoulou, A., Tillmann, S., Koschmieder, S., and Weiskirchen, R. (2020). TNF-\u03b1 controls Lipocalin-2 expression in PC-3 prostate cancer cells. Cytokine, 135.","DOI":"10.1016\/j.cyto.2020.155214"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Weider, M., Schr\u00f6der, A., Docheva, D., Rodrian, G., Enderle, I., Seidel, C.L., Andreev, D., Wegner, M., Bozec, A., and Deschner, J. (2020). A human periodontal ligament fibroblast cell line as a new model to study periodontal stress. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21217961"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1177\/1753425913505121","article-title":"High-mobility group box protein-1 released by human-periodontal ligament cells modulates macrophage migration and activity in vitro","volume":"20","author":"Wolf","year":"2014","journal-title":"Innate Immun."},{"key":"ref_29","first-page":"13","article-title":"Molecular Biology of Orthodontic Tooth Movement Orthodontic Tooth Movement and ECM Remodeling Role of Cytokines, Growth Factors and","volume":"1","author":"Nayak","year":"2013","journal-title":"J. Dent. Oral Health"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.1007\/s00784-019-03111-8","article-title":"Orthodontic cell stress modifies proinflammatory cytokine expression in human PDL cells and induces immunomodulatory effects via TLR-4 signaling in vitro","volume":"24","author":"Marciniak","year":"2020","journal-title":"Clin. Oral Investig."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1089\/dna.2010.1139","article-title":"Analysis of gene expression profile of periodontal ligament cells subjected to cyclic compressive force","volume":"30","author":"Wu","year":"2011","journal-title":"DNA Cell Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"26743","DOI":"10.1074\/jbc.M111.233700","article-title":"The interaction between nesprins and sun proteins at the nuclear envelope is critical for force transmission between the nucleus and cytoskeleton","volume":"286","author":"Lombardi","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1016\/j.cell.2006.09.044","article-title":"Force Sensing by Mechanical Extension of the Src Family Kinase Substrate p130Cas","volume":"127","author":"Sawada","year":"2006","journal-title":"Cell"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1083\/jcb.200505018","article-title":"Mechanical force mobilizes zyxin from focal adhesions to actin filaments and regulates cytoskeletal reinforcement","volume":"171","author":"Yoshigi","year":"2005","journal-title":"J. Cell Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1846","DOI":"10.1091\/mbc.e11-12-1057","article-title":"Stretch-induced actin remodeling requires targeting of zyxin to stress fibers and recruitment of actin regulators","volume":"23","author":"Hoffman","year":"2012","journal-title":"Mol. Biol. Cell"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Blawat, K., Mayr, A., Hardt, M., Kirschneck, C., Nokhbehsaim, M., Behl, C., Deschner, J., J\u00e4ger, A., and Memmert, S. (2020). Regulation of autophagic signaling by mechanical loading and inflammation in human PDL fibroblasts. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21249446"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2933","DOI":"10.1007\/s00784-018-2381-6","article-title":"Damage-regulated autophagy modulator 1 in oral inflammation and infection","volume":"22","author":"Memmert","year":"2018","journal-title":"Clin. Oral Investig."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.aanat.2018.09.006","article-title":"Role of HSP70 protein in human periodontal ligament cell function and physiology","volume":"221","author":"Wolf","year":"2019","journal-title":"Ann. Anat."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1007\/s00784-015-1580-7","article-title":"Short-term heat pre-treatment modulates the release of HMGB1 and pro-inflammatory cytokines in hPDL cells following mechanical loading and affects monocyte behavior","volume":"20","author":"Wolf","year":"2016","journal-title":"Clin. Oral Investig."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1111\/jre.12741","article-title":"Advanced glycation end-products increase lipocalin 2 expression in human oral epithelial cells","volume":"55","author":"Kido","year":"2020","journal-title":"J. Periodontal Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e20200276","DOI":"10.1590\/1678-7757-2020-0276","article-title":"Increase in serum and salivary neutrophil gelatinase-associated lipocalin levels with increased periodontal inflammation","volume":"28","author":"Tan","year":"2020","journal-title":"J. Appl. Oral Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1002\/hep.27930","article-title":"Lipocalin-2 (NGAL\/LCN2), a \u201cHelp-Me\u201d Signal in Organ Inflammation","volume":"63","author":"Asimakopoulou","year":"2016","journal-title":"Hepatology"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.yexmp.2007.03.004","article-title":"Acute endotoxemia is associated with upregulation of lipocalin 24p3\/Lcn2 in lung and liver","volume":"83","author":"Sunil","year":"2007","journal-title":"Exp. Mol. Pathol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.celrep.2019.03.031","article-title":"PCNA-Mediated Degradation of p21 Coordinates the DNA Damage Response and Cell Cycle Regulation in Individual Cells","volume":"27","author":"Sheng","year":"2019","journal-title":"Cell Rep."},{"key":"ref_45","first-page":"2473","article-title":"Mcm-2 protein expression predicts prognosis better than Ki-67 antigen in oral cavity squamocellular carcinoma","volume":"26","author":"Szelachowska","year":"2006","journal-title":"Anticancer Res."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/11\/7\/932\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:21:55Z","timestamp":1760163715000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/11\/7\/932"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,23]]},"references-count":45,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2021,7]]}},"alternative-id":["biom11070932"],"URL":"https:\/\/doi.org\/10.3390\/biom11070932","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,23]]}}}