{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T05:03:14Z","timestamp":1780376594974,"version":"3.54.1"},"reference-count":44,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T00:00:00Z","timestamp":1768348800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006141","name":"Military University of Technology","doi-asserted-by":"crossref","award":["UGB 502-000013-W100-22"],"award-info":[{"award-number":["UGB 502-000013-W100-22"]}],"id":[{"id":"10.13039\/501100006141","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100009687","name":"Wroclaw Medical University","doi-asserted-by":"crossref","award":["SUBZ.B190.25.024"],"award-info":[{"award-number":["SUBZ.B190.25.024"]}],"id":[{"id":"10.13039\/501100009687","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100009687","name":"Wroclaw Medical University","doi-asserted-by":"crossref","award":["SUBZ.B031.25.011"],"award-info":[{"award-number":["SUBZ.B031.25.011"]}],"id":[{"id":"10.13039\/501100009687","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100009687","name":"Wroclaw Medical University","doi-asserted-by":"crossref","award":["SUBZ.B033.25.014"],"award-info":[{"award-number":["SUBZ.B033.25.014"]}],"id":[{"id":"10.13039\/501100009687","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Medical University in Bialystok"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Background: Mechanical loading is a fundamental regulator of bone remodelling; however, the mechanotransduction mechanisms governing alveolar bone adaptation under tensile-dominant orthodontic loading remain insufficiently defined. In particular, the molecular pathways associated with tension-driven cortical modelling in the periodontal ligament (PDL)\u2013bone complex have not been systematically interpreted in the context of advanced biomechanical simulations. Methods: A nonlinear finite element model of the alveolar bone\u2013PDL\u2013tooth complex was developed using patient-specific CBCT data. Three loading configurations were analysed: (i) conventional orthodontic loading, (ii) loading combined with corticotomy alone, and (iii) a translation-dominant configuration generated by the Bone Protection System (BPS). Pressure distribution, displacement vectors, and stress polarity within the PDL and cortical plate were quantified across different bone density conditions. The mechanical outputs were subsequently interpreted in relation to established mechanotransductive molecular pathways involved in osteogenesis and angiogenesis. Results: Conventional loading generated compression-dominant stress fields within the marginal PDL, frequently exceeding physiological thresholds and producing moment-driven root displacement. Corticotomy alone reduced local stiffness but did not substantially alter stress polarity. The BPS configuration redirected loads toward a tensile-favourable mechanical environment characterised by reduced peak compressive pressures and parallel (translation-dominant) displacement vectors. The predicted tensile stress distribution is compatible with activation profiles of key mechanosensitive pathways, including integrin\u2013FAK signalling, Wnt\/\u03b2-catenin\u2013mediated osteogenic differentiation and HIF-1\u03b1\/VEGF-driven angiogenic coupling, suggesting a microenvironment that may be more conducive to cortical apposition than to resorption. Conclusions: This study presents a computational\u2013molecular framework linking finite element\u2013derived tensile stress patterns with osteogenic and angiogenic signalling pathways relevant to alveolar bone remodelling. The findings suggestthat controlled redirection of orthodontic loading toward tensile domains may shift the mechanical environment of the PDL\u2013bone complex toward conditions associated with osteogenic than resorptive responses providing a mechanistic basis for tension-induced cortical modelling. This mechanobiological paradigm advances the understanding of load-guided alveolar bone adaptation at both the tissue and molecular levels.<\/jats:p>","DOI":"10.3390\/biom16010150","type":"journal-article","created":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T15:12:04Z","timestamp":1768403524000},"page":"150","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Mechanobiological Regulation of Alveolar Bone Remodeling: A Finite Element Study and Molecular Pathway Interpretation"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5281-0940","authenticated-orcid":false,"given":"Anna Ewa","family":"Kuc","sequence":"first","affiliation":[{"name":"Department of Dentofacial Orthopedics and Orthodontics, Wroclaw Medical University, 50-425 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4326-8907","authenticated-orcid":false,"given":"Magdalena","family":"Sulewska","sequence":"additional","affiliation":[{"name":"Department of Periodontal and Oral Mucosa Diseases, Medical University of Bialystok, ul. Waszyngtona 13, 15-269 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3362-216X","authenticated-orcid":false,"given":"Kamil","family":"Sybilski","sequence":"additional","affiliation":[{"name":"Faculty of Mechanical Engineering, Military University of Technology, 00-908 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5781-6540","authenticated-orcid":false,"given":"Jacek","family":"Kotu\u0142a","sequence":"additional","affiliation":[{"name":"Department of Dentofacial Orthopedics and Orthodontics, Wroclaw Medical University, 50-425 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grzegorz","family":"Hajduk","sequence":"additional","affiliation":[{"name":"Chair and Department of Oral Surgery, Medical University of Lublin, Witolda Chod\u017aki 6 Street, 20-093 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2021-3743","authenticated-orcid":false,"given":"Szymon","family":"Saternus","sequence":"additional","affiliation":[{"name":"Faculty of Mechanical Engineering, Military University of Technology, 00-908 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1300-8020","authenticated-orcid":false,"given":"Jerzy","family":"Ma\u0142achowski","sequence":"additional","affiliation":[{"name":"Faculty of Mechanical Engineering, Military University of Technology, 00-908 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3811-4834","authenticated-orcid":false,"given":"Julia","family":"Bar","sequence":"additional","affiliation":[{"name":"Department of Immunopathology and Molecular Biology, Wroclaw Medical University, 50-556 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Lis","sequence":"additional","affiliation":[{"name":"Department of Dentofacial Orthopedics and Orthodontics, Wroclaw Medical University, 50-425 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3284-7893","authenticated-orcid":false,"given":"Beata","family":"Kawala","sequence":"additional","affiliation":[{"name":"Department of Dentofacial Orthopedics and Orthodontics, Wroclaw Medical University, 50-425 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2518-0007","authenticated-orcid":false,"given":"Micha\u0142","family":"Sarul","sequence":"additional","affiliation":[{"name":"Department of Integrated Dentistry, Wroclaw Medical University, 50-425 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"324","DOI":"10.2319\/022521-156.1","article-title":"Effect of orthodontic treatment on periodontal health of periodontally compromised patients","volume":"92","author":"Gehlot","year":"2022","journal-title":"Angle Orthod."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"S2","DOI":"10.4103\/jpbs.JPBS_549_20","article-title":"Extraction or Nonextraction in Orthodontic Cases: A Review","volume":"13","author":"Mapare","year":"2021","journal-title":"J. Pharm. Bioallied Sci."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Brugnami, F., Caiazzo, A., and Meuli, S. (2024). From Corticotomy to Orthodontically Driven Osteogenesis: Surgical Considerations. Orthodontically Driven Osteogenesis, Wiley. [1st ed.]. Available online: https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/9781119700593.ch3.","DOI":"10.1002\/9781119700593"},{"key":"ref_4","first-page":"11","article-title":"Interactions between Orthodontic Treatment and Gingival Tissue","volume":"26","author":"Liu","year":"2023","journal-title":"Chin. J. Dent. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1590\/2177-6709.24.4.034-045.oar","article-title":"Effect of orthodontic treatment on alveolar bone thickness in adults: A systematic review","volume":"24","author":"Sendyk","year":"2019","journal-title":"Dent. Press. J. Orthod."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"251","DOI":"10.4103\/2321-1407.190736","article-title":"Maxillary bone defects and their relationship to transverse maxillary discrepancies","volume":"6","year":"2016","journal-title":"APOS"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"174","DOI":"10.25259\/APOS_124_2021","article-title":"Age-related osteogenesis on lateral force application to rat incisor\u2014Part II: Bony recession and cortical remodeling","volume":"11","author":"Kim","year":"2021","journal-title":"APOS"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1111\/prd.12484","article-title":"Complications and treatment errors involving periodontal tissues related to orthodontic therapy","volume":"92","author":"Jepsen","year":"2023","journal-title":"Periodontol. 2000"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/0889-5406(87)90455-0","article-title":"Orthodontic relapse, apical root resorption, and crestal alveolar bone levels","volume":"91","author":"Sharpe","year":"1987","journal-title":"Am. J. Orthod. Dentofac. Orthop."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1590\/2177-6709.21.3.018-029.oin","article-title":"Gingival recession: Its causes and types, and the importance of orthodontic treatment","volume":"21","author":"Jati","year":"2016","journal-title":"Dent. Press. J. Orthod."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"653","DOI":"10.2319\/060806-234","article-title":"Periodontal ligament hydrostatic pressure with areas of root resorption after application of a continuous torque moment","volume":"77","author":"Hohmann","year":"2007","journal-title":"Angle Orthod."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1631\/jzus.B1700195","article-title":"A biomechanical case study on the optimal orthodontic force on the maxillary canine tooth based on finite element analysis","volume":"19","author":"Wu","year":"2018","journal-title":"J. Zhejiang Univ. Sci. B"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Kuc, A.E., Kulgawczyk, M., Sulewska, M.E., Kuc, N., Kawala, B., Lis, J., Sarul, M., and Kotu\u0142a, J. (2024). The Effect of Corticotomy-Assisted Orthodontic Therapy (CAOT) or Periodontally Accelerated Osteogenic Orthodontics (PAOO) on Bone Remodeling and the Health of Periodontium: A Systematic Review of Systematic Reviews. JCM, 13.","DOI":"10.3390\/jcm13195726"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Park, W.B., Park, W., Lim, S.W., and Han, J.Y. (2023). Periodontal Phenotype Modification Using Subepithelial Connective Tissue Graft and Bone Graft in the Mandibular Anterior Teeth with Mucogingival Problems Following Orthodontic Treatment. Medicina, 59.","DOI":"10.3390\/medicina59030584"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/S8756-3282(01)00642-1","article-title":"Targeted and nontargeted bone remodeling: Relationship to basic multicellular unit origination and progression","volume":"30","author":"Parfitt","year":"2002","journal-title":"Bone"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Pietro\u0144, K., Mazurkiewicz, \u0141., Sybilski, K., and Ma\u0142achowski, J. (2022). Correlation of Bone Material Model Using Voxel Mesh and Parametric Optimization. Materials, 15.","DOI":"10.3390\/ma15155163"},{"key":"ref_17","unstructured":"Mart\u00ednez, S.M., Lenz, J., Schweizerhof, K., and Schindler, H.J. (2015, January 15\u201317). A Variable Finite Element Model of the Overall Human Masticatory System for Evaluation of Stress Distributions during Biting and Bruxism. Proceedings of the 10th European LS-DYNA Conference 2015, W\u00fcrzburg, Germany."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Kuc, A.E., Sybilski, K., Kotu\u0142a, J., Pi\u0105tkowski, G., Kowala, B., Lis, J., Saternus, S., and Sarul, M. (2024). The Hydrostatic Pressure Distribution in the Periodontal Ligament and the Risk of Root Resorption\u2014A Finite Element Method (FEM) Study on the Nonlinear Innovative Model. Materials, 17.","DOI":"10.3390\/ma17071661"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Kuc, A.E., Sybilski, K., Stankiewicz, M., Kotu\u0142a, J., Kuc, N., Hajduk, G., Ma\u0142achowski, J., and Sarul, M. (2025). The Influence of Bone Density on Stresses in the Periodontal Ligament During Orthodontic Movement-Finite Element Study on Innovative Model. Materials, 18.","DOI":"10.3390\/ma18040776"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1038\/s41413-022-00190-4","article-title":"Mechanical regulation of bone remodeling","volume":"10","author":"Wang","year":"2022","journal-title":"Bone Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1016\/j.bone.2003.12.024","article-title":"Activation of the transcription factor HIF-1 and its target genes, VEGF, HO-1, iNOS, during fracture repair","volume":"34","author":"Komatsu","year":"2004","journal-title":"Bone"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1111\/j.1601-6343.2009.01444.x","article-title":"RANK\/RANKL\/OPG during orthodontic tooth movement","volume":"12","author":"Yamaguchi","year":"2009","journal-title":"Orthod. Craniofac. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1038\/s41413-022-00223-y","article-title":"Biomechanics and mechanobiology of the bone matrix","volume":"10","author":"Ma","year":"2022","journal-title":"Bone Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1038\/s41421-024-00689-6","article-title":"Cell signaling and transcriptional regulation of osteoblast lineage commitment, differentiation, bone formation, and homeostasis","volume":"10","author":"Zhu","year":"2024","journal-title":"Cell Discov."},{"key":"ref_25","first-page":"16","article-title":"The biology of distraction osteogenesis for correction of mandibular and craniomaxillofacial defects: A review","volume":"11","author":"Natu","year":"2014","journal-title":"Dent. Res. J. (Isfahan)"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"402","DOI":"10.2174\/0113892010289575240306033011","article-title":"TP508 Promotes Bone Regeneration on Distraction Osteogenesis via the Activation of Wnt\/\u03b2-catenin Signaling Pathway","volume":"26","author":"Li","year":"2025","journal-title":"Curr. Pharm. Biotechnol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1359\/jbmr.1998.13.8.1221","article-title":"Expression of bone matrix proteinmRNA during distraction osteogenesis","volume":"13","author":"Sato","year":"1998","journal-title":"J. Bone Miner. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1111\/j.1601-0825.2007.01388.x","article-title":"The BMP signaling and its Smads in mandibular distraction osteogenesis","volume":"14","author":"Khanal","year":"2008","journal-title":"Oral. Dis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.gene.2012.04.076","article-title":"Mechanical regulation of signaling pathways in bone","volume":"503","author":"Thompson","year":"2012","journal-title":"Gene"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1053\/j.sodo.2024.01.012","article-title":"Accelerated orthodontics (AO): The past, present and the future","volume":"30","author":"Gandedkar","year":"2024","journal-title":"Semin. Orthod."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Tsolakis, I.A., Christopoulou, I., Sitaras, S., Lyros, I., Rontogianni, A., Dalampira, M., and Tsolakis, A.I. (2023). Molecular and Biological Aspects of Orthodontic Tooth Movement: Possibilities for Bioengineering Intervention: A Narrative Review. Bioengineering, 10.","DOI":"10.3390\/bioengineering10111275"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1159\/000351897","article-title":"Regional Acceleratory Phenomenon","volume":"18","author":"Verna","year":"2016","journal-title":"Front. Oral. Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/j.procbio.2022.04.033","article-title":"Bone formation and bone repair: The roles and crosstalk of osteoinductive signaling pathways","volume":"118","author":"Jing","year":"2022","journal-title":"Process Biochem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"594","DOI":"10.3892\/ijmm.2016.2636","article-title":"Mechanical strain promotes osteoblastic differentiation through integrin-\u03b21-mediated \u03b2-catenin signaling","volume":"38","author":"Yan","year":"2016","journal-title":"Int. J. Mol. Med."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Liu, R., Huang, L., Xiao, X., Guan, Y., Jiang, Y., Yin, X., Zou, S., and Ye, Q. (2020). Biomechanical Interfaces of Corticotomies on Periodontal Tissue Remodeling during Orthodontic Tooth Movement. Coatings, 11.","DOI":"10.3390\/coatings11010001"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1380","DOI":"10.1097\/SCS.0000000000003625","article-title":"Biology of Bone Formation, Fracture Healing, and Distraction Osteogenesis","volume":"28","author":"Runyan","year":"2017","journal-title":"J. Craniofac. Surg."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Kim, J.M., Lin, C., Stavre, Z., Greenblatt, M.B., and Shim, J.H. (2020). Osteoblast-Osteoclast Communication and Bone Homeostasis. Cells, 9.","DOI":"10.3390\/cells9092073"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1111\/j.1600-0722.2006.00400.x","article-title":"Interleukin-1alpha and tumor necrosis factor-alpha expression during the early phases of orthodontic tooth movement in rats","volume":"114","author":"Bletsa","year":"2006","journal-title":"Eur. J. Oral. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"152","DOI":"10.22203\/eCM.v032a10","article-title":"The crucial role of neutrophil granulocytes in bone fracture healing","volume":"32","author":"Kovtun","year":"2016","journal-title":"Eur. Cell Mater."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Kargozar, S., Mozafari, M., Hamzehlou, S., Brouki Milan, P., Kim, H.W., and Baino, F. (2019). Bone Tissue Engineering Using Human Cells: A Comprehensive Review on Recent Trends, Current Prospects, and Recommendations. Appl. Sci., 9.","DOI":"10.3390\/app9010174"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"101111","DOI":"10.1016\/j.mtbio.2024.101111","article-title":"Establishing stable and highly osteogenic hiPSC-derived MSCs for 3D-printed bone graft through microenvironment modulation by CHIR99021-treated osteocytes","volume":"26","author":"Guo","year":"2024","journal-title":"Mater. Today Bio"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Wang, L., Ruan, M., Bu, Q., and Zhao, C. (2025). Signaling Pathways Driving MSC Osteogenesis: Mechanisms, Regulation, and Translational Applications. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26031311"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1210\/endrev\/bnad008","article-title":"Signaling Pathways of the Insulin-like Growth Factor Binding Proteins","volume":"44","author":"Baxter","year":"2023","journal-title":"Endocr. Rev."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"124125","DOI":"10.1016\/j.ijbiomac.2023.124125","article-title":"The role of insulin-like growth factor-1 in bone remodeling: A review","volume":"238","author":"Fang","year":"2023","journal-title":"Int. J. Biol. Macromol."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/1\/150\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T06:39:39Z","timestamp":1768545579000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/1\/150"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,14]]},"references-count":44,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["biom16010150"],"URL":"https:\/\/doi.org\/10.3390\/biom16010150","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,14]]}}}