{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T15:05:24Z","timestamp":1791644724128,"version":"4.3.4"},"reference-count":165,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2025,8,23]],"date-time":"2025-08-23T00:00:00Z","timestamp":1755907200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Orthodontic tooth movement (OTM) is accompanied by sterile inflammation, a necessary biological process that facilitates tooth displacement but also contributes to adverse effects, including hyalinization and orthodontically induced external apical root resorption (OEARR). Despite advancements in orthodontic therapies, the inflammatory response\u2014regulated by dynamic interactions between tissue-specific cells and their molecular mediators\u2014remains a critical factor influencing treatment outcomes. This review summarizes the current understanding of the cellular and molecular mechanisms underlying OTM, with a focus on how these insights can support the development of targeted therapeutic strategies. These include cell- and molecule-based therapies, biomaterial-mediated delivery systems, and applications of artificial intelligence (AI). Notably, AI offers promising opportunities for modeling and simulating biological responses, enabling the optimization of individualized treatment planning. We further discuss current clinical practices and highlight emerging experimental findings, with an emphasis on unresolved research questions pivotal to improving therapeutic efficacy and reducing complications such as OEARR. This comprehensive overview aims to inform future directions in orthodontics by integrating mechanistic knowledge with technological innovation.<\/jats:p>","DOI":"10.3390\/ijms26178203","type":"journal-article","created":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T00:10:36Z","timestamp":1756080636000},"page":"8203","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Shaping Orthodontics of the Future: Concepts and Implications from a Cellular and Molecular Perspective"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1924-2694","authenticated-orcid":false,"given":"Thorsten","family":"Steinberg","sequence":"first","affiliation":[{"name":"Center for Dental Medicine, Division of Oral Biotechnology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Hugstetterstr. 55, 79106 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Britta","family":"Jung","sequence":"additional","affiliation":[{"name":"Center for Dental Medicine, Department of Orthodontics, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Hugstetterstr. 55, 79106 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayman","family":"Husari","sequence":"additional","affiliation":[{"name":"Center for Dental Medicine, Department of Orthodontics, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Hugstetterstr. 55, 79106 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuoqiu","family":"Bai","sequence":"additional","affiliation":[{"name":"Center for Dental Medicine, Division of Oral Biotechnology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Hugstetterstr. 55, 79106 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal","family":"Tomakidi","sequence":"additional","affiliation":[{"name":"Center for Dental Medicine, Division of Oral Biotechnology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Hugstetterstr. 55, 79106 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e23499","DOI":"10.1002\/dvg.23499","article-title":"Novel approaches for periodontal tissue engineering","volume":"60","author":"Swanson","year":"2022","journal-title":"Genesis"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"107","DOI":"10.25077\/ar.10.1.107-115.2023","article-title":"Speech production and malocclusion: A review","volume":"10","author":"Handoko","year":"2023","journal-title":"J. Arbitrer"},{"key":"ref_3","first-page":"e30453","article-title":"The impact of orthodontic treatment on masticatory performance: A literature review","volume":"14","author":"Zanon","year":"2022","journal-title":"Cureus"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Maltha, J.C., Krishnan, V., and Kuijpers-Jagtman, A.M. (2021). Cellular and molecular biology of orthodontic tooth movement. Biol. Mech. Tooth Mov., 33\u201348.","DOI":"10.1002\/9781119608912.ch3"},{"key":"ref_5","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_6","doi-asserted-by":"crossref","unstructured":"Nile, M., Folwaczny, M., Wichelhaus, A., Baumert, U., and Janjic Rankovic, M. (2023). Fluid flow shear stress and tissue remodeling\u2014An orthodontic perspective: Evidence synthesis and differential gene expression network analysis. Front. Bioeng. Biotechnol., 11.","DOI":"10.3389\/fbioe.2023.1256825"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2331","DOI":"10.1039\/D2CP05051J","article-title":"Chemical bonds in collagen rupture selectively under tensile stress","volume":"25","author":"Rowe","year":"2023","journal-title":"Phys. Chem. Chem. Phys."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s12953-019-0151-2","article-title":"Proteomic analysis of human periodontal ligament cells under hypoxia","volume":"17","author":"Li","year":"2019","journal-title":"Proteome Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"430","DOI":"10.3892\/etm.2021.9847","article-title":"Dynamic study into autophagy and apoptosis during orthodontic tooth movement","volume":"21","author":"Wang","year":"2021","journal-title":"Exp. Ther. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"9710","DOI":"10.1111\/jcmm.16920","article-title":"Hypoxia-inducible factor 1-alpha acts as a bridge factor for crosstalk between ERK1\/2 and caspases in hypoxia-induced apoptosis of cementoblasts","volume":"25","author":"Yong","year":"2021","journal-title":"J. Cell. Mol. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"20388","DOI":"10.1073\/pnas.0908698106","article-title":"Necrotic cells trigger a sterile inflammatory response through the Nlrp3 inflammasome","volume":"106","author":"Iyer","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_12","first-page":"2814015","article-title":"Effects of compressive and tensile strain on macrophages during simulated orthodontic tooth movement","volume":"2020","author":"Nazet","year":"2020","journal-title":"Mediat. Inflamm."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"412","DOI":"10.4236\/ojst.2014.48055","article-title":"Expression of MMP-9 and-13 on the Pressure Side under Orthodontic Loading","volume":"4","author":"Mah","year":"2014","journal-title":"Open J. Stomatol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Rosenblum, G., Van den Steen, P.E., Cohen, S.R., Bitler, A., Brand, D.D., Opdenakker, G., and Sagi, I. (2010). Direct visualization of protease action on collagen triple helical structure. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0011043"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Behm, C., Zhao, Z., and Andrukhov, O. (2022). Immunomodulatory activities of periodontal ligament stem cells in orthodontic forces-induced inflammatory processes: Current views and future perspectives. Front. Oral. Health, 3.","DOI":"10.3389\/froh.2022.877348"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Xu, H., Zhang, S., Sathe, A.A., Jin, Z., Guan, J., Sun, W., Xing, C., Zhang, H., and Yan, B. (2022). CCR2+ Macrophages promote orthodontic tooth movement and alveolar bone remodeling. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.835986"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1186\/s40510-024-00537-z","article-title":"Breaking a dogma: Orthodontic tooth movement alters systemic immunity","volume":"25","author":"Klein","year":"2024","journal-title":"Prog. Orthod."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1007\/s12598-024-02884-6","article-title":"A novel Nb\u2013TiNb nanocomposite with single-phase BCC structure for bio-implant applications","volume":"44","author":"Liu","year":"2025","journal-title":"Rare Met."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"S1267","DOI":"10.4103\/jpbs.jpbs_82_25","article-title":"Exploring the Role of Exosomes in Accelerating Orthodontic Tooth Movement","volume":"17","author":"Zwiri","year":"2025","journal-title":"J. Pharm. Bioallied Sci."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Xu, B., Peng, C., Du, Y., Li, Q., and Yang, K. (2024). Effect of autophagy on aging-related changes in orthodontic tooth movement in rats. BMC Oral. Health, 24.","DOI":"10.1186\/s12903-024-04549-3"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"469.e461","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_22","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_23","unstructured":"Proffit, W.R., Fields, H., Larson, B., and Sarver, D.M. (2018). Contemporary Orthodontics-E-Book: Contemporary Orthodontics-E-Book, Elsevier Health Sciences."},{"key":"ref_24","unstructured":"Kraus, B.S., and Riedel, R.A. (1962). The Biomechanics of Tooth Movement. Vistas in Orthodontics, Lea & Febiger."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"S325","DOI":"10.4103\/0975-7406.163437","article-title":"Biomarkers in orthodontic tooth movement","volume":"7","author":"Kumar","year":"2015","journal-title":"J. Pharm. Bioallied Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/S0889-5406(96)70082-3","article-title":"Magnitude of orthodontic forces and rate of bodily tooth movement. An experimental study","volume":"110","author":"Pilon","year":"1996","journal-title":"Am. J. Orthod. Dentofac. Orthop."},{"key":"ref_27","first-page":"156","article-title":"Mechanobiology of orthodontic tooth movement: An update","volume":"12","author":"Maltha","year":"2023","journal-title":"J. World Fed. Orthod."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Rajpar, I., Kumar, G., Fortina, P., and Tomlinson, R.E. (2022). Toll-like receptor 4 signaling in osteoblasts is required for load-induced bone formation in mice. bioRxiv, 2022.2008.2005.502963.","DOI":"10.1101\/2022.08.05.502963"},{"key":"ref_29","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_30","doi-asserted-by":"crossref","unstructured":"Roth, C.E., Craveiro, R.B., Niederau, C., Malyaran, H., Neuss, S., Jankowski, J., and Wolf, M. (2022). Mechanical compression by simulating orthodontic tooth movement in an in vitro model modulates phosphorylation of AKT and MAPKs via TLR4 in human periodontal ligament cells. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23158062"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"630","DOI":"10.22271\/oral.2022.v8.i2i.1568","article-title":"RANK-RANKL-OPG: A current trends in orthodontic tooth movement and its role in accelerated orthodontics","volume":"8","author":"Kumar","year":"2022","journal-title":"Int. J. Appl. Dent. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"105873","DOI":"10.1155\/2013\/105873","article-title":"Biomarkers of periodontal tissue remodeling during orthodontic tooth movement in mice and men: Overview and clinical relevance","volume":"2013","author":"Cappabianca","year":"2013","journal-title":"Sci. World J."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2713","DOI":"10.1038\/s41467-021-22979-3","article-title":"The ubiquitylation of IL-1\u03b2 limits its cleavage by caspase-1 and targets it for proteasomal degradation","volume":"12","author":"Vijayaraj","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Zhen, H., Hu, Y., Liu, X., Fan, G., and Zhao, S. (2024). The protease caspase-1: Activation pathways and functions. Biochem. Biophys. Res. Commun., 717.","DOI":"10.1016\/j.bbrc.2024.149978"},{"key":"ref_35","first-page":"100130","article-title":"Matrix metalloproteinase-8 (MMP-8) and its inhibitors: A minireview","volume":"10","author":"Baidya","year":"2024","journal-title":"Eur. J. Med. Chem. Rep."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"174","DOI":"10.2144\/000114597","article-title":"An Improved Collagen Zymography Approach for Evaluating the Collagenases MMP-1, MMP-8, and MMP-13","volume":"63","author":"Inanc","year":"2017","journal-title":"BioTechniques"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1016\/j.sdentj.2020.07.001","article-title":"Quantification of matrix metalloproteinases MMP-8 and MMP-9 in gingival overgrowth","volume":"33","year":"2021","journal-title":"Saudi Dent. J."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Luchian, I., Moscalu, M., Goriuc, A., Nucci, L., Tatarciuc, M., Martu, I., and Covasa, M. (2021). Using salivary MMP-9 to successfully quantify periodontal inflammation during orthodontic treatment. J. Clin. Med., 10.","DOI":"10.3390\/jcm10030379"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Charzewski, \u0141., Krzy\u015bko, K.A., and Lesyng, B. (2021). Structural characterisation of inhibitory and non-inhibitory MMP-9\u2013TIMP-1 complexes and implications for regulatory mechanisms of MMP-9. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-92881-x"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"9462","DOI":"10.1021\/bi0260132","article-title":"The \u03a4umor necrosis factor-\u03b1 converting enzyme (TACE): A unique metalloproteinase with highly defined substrate selectivity","volume":"41","author":"Mohan","year":"2002","journal-title":"Biochemistry"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Behm, C., Nemec, M., Blufstein, A., Schubert, M., Rausch-Fan, X., Andrukhov, O., and Jonke, E. (2021). Interleukin-1\u03b2 Induced Matrix Metalloproteinase Expression in Human Periodontal Ligament-Derived Mesenchymal Stromal Cells under In Vitro Simulated Static Orthodontic Forces. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22031027"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1093\/ejo\/cjs057","article-title":"Induction of cytokines, MMP9, TIMPs, RANKL and OPG during orthodontic tooth movement","volume":"35","author":"Grant","year":"2013","journal-title":"Eur. J. Orthod."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Behm, C., Nemec, M., Weissinger, F., Rausch, M.A., Andrukhov, O., and Jonke, E. (2021). MMPs and TIMPs expression levels in the periodontal ligament during orthodontic tooth movement: A systematic review of in vitro and in vivo studies. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22136967"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1038\/s41368-024-00284-1","article-title":"The osteoclastic activity in apical distal region of molar mesial roots affects orthodontic tooth movement and root resorption in rats","volume":"16","author":"Zheng","year":"2024","journal-title":"Int. J. Oral. Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1177\/0022034514553817","article-title":"Enhanced M1\/M2 macrophage ratio promotes orthodontic root resorption","volume":"94","author":"He","year":"2015","journal-title":"J. Dent. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"8","DOI":"10.5466\/ijoms.16.8","article-title":"Expression of IL-34 in Root Resorption by Excessive Orthodontic Force","volume":"16","author":"Kohno","year":"2017","journal-title":"Int. J. Oral-Med. Sci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1007\/s10753-018-00951-6","article-title":"Effects of IL-1\u03b2 on MMP-9 Expression in Cementoblast-Derived Cell Line and MMP-Mediated Degradation of Type I Collagen","volume":"42","author":"Du","year":"2019","journal-title":"Inflammation"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1172\/JCI200523394","article-title":"IL-1 mediates TNF-induced osteoclastogenesis","volume":"115","author":"Wei","year":"2005","journal-title":"J. Clin. Investig."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"284","DOI":"10.4041\/kjod24.030","article-title":"Genetic polymorphisms in external apical root resorption and orthodontic tooth movements: A systematic review","volume":"54","author":"Maia","year":"2024","journal-title":"Korean J. Orthod."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1111\/odi.12185","article-title":"Polymorphisms of genes encoding P 2 X 7R, IL-1 B, OPG and RANK in orthodontic-induced apical root resorption","volume":"20","author":"Pereira","year":"2014","journal-title":"Oral. Dis."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e17841","DOI":"10.1016\/j.heliyon.2023.e17841","article-title":"Cilengitide inhibits osteoclast adhesion through blocking the \u03b1v\u03b23-mediated FAK\/Src signaling pathway","volume":"9","author":"Guo","year":"2023","journal-title":"Heliyon"},{"key":"ref_52","first-page":"1","article-title":"NF-\u03baB-direct activation of microRNAs with repressive effects on monocyte-specific genes is critical for osteoclast differentiation","volume":"16","author":"Comet","year":"2015","journal-title":"Genome Biol."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Eom, J., Yoo, J., Kim, J.J., Lee, J.B., Choi, W., Park, C.G., and Seo, J.-Y. (2018). Viperin deficiency promotes polarization of macrophages and secretion of M1 and M2 cytokines. Immune Netw., 18.","DOI":"10.4110\/in.2018.18.e32"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Lelios, I., Cansever, D., Utz, S.G., Mildenberger, W., Stifter, S.A., and Greter, M. (2020). Emerging roles of IL-34 in health and disease. J. Exp. Med., 217.","DOI":"10.1084\/jem.20190290"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"4575","DOI":"10.1038\/s41598-021-84354-y","article-title":"RANKL\/OPG ratio regulates odontoclastogenesis in damaged dental pulp","volume":"11","author":"Nishida","year":"2021","journal-title":"Scientif. Rep."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"AlQranei, M.S., Aljohani, H., Majumdar, S., Senbanjo, L.T., and Chellaiah, M.A. (2020). C-phycocyanin attenuates RANKL-induced osteoclastogenesis and bone resorption in vitro through inhibiting ROS levels, NFATc1 and NF-\u03baB activation. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-59363-y"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/j.bone.2006.09.023","article-title":"The molecular understanding of osteoclast differentiation","volume":"40","author":"Asagiri","year":"2007","journal-title":"Bone"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"35","DOI":"10.3803\/EnM.2015.30.1.35","article-title":"NF-\u03baB-mediated regulation of osteoclastogenesis","volume":"30","author":"Boyce","year":"2015","journal-title":"Endocrinol. Metab."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1002\/jbmr.1739","article-title":"Negative regulation of osteoclast precursor differentiation by CD11b and \u03b2 2 integrin-B-cell lymphoma 6 signaling","volume":"28","author":"Lee","year":"2013","journal-title":"J. Bone Miner. Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.yexcr.2006.10.001","article-title":"RANK ligand signaling modulates the matrix metalloproteinase-9 gene expression during osteoclast differentiation","volume":"313","author":"Sundaram","year":"2007","journal-title":"Exp. Cell Res."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Omata, Y., Tachibana, H., Aizaki, Y., Mimura, T., and Sato, K. (2023). Essentiality of Nfatc1 short isoform in osteoclast differentiation and its self-regulation. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-45909-3"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Kanzaki, H., Wada, S., Yamaguchi, Y., Katsumata, Y., Itohiya, K., and Fukaya, S. (2019). Compression and tension variably alter Osteoprotegerin expression via miR-3198 in periodontal ligament cells. BMC Mol. Cell Biol., 20.","DOI":"10.1186\/s12860-019-0187-2"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1186\/1757-2215-5-34","article-title":"Osteoprotegerin (OPG) protects ovarian cancer cells from TRAIL-induced apoptosis but does not contribute to malignant ascites-mediated attenuation of TRAIL-induced apoptosis","volume":"5","author":"Lane","year":"2012","journal-title":"J. Ovarian Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"31","DOI":"10.4236\/ojapo.2013.23005","article-title":"TRAIL Immunolocalisation in the Rat Periodontal Ligament during Experimental Tooth Movement. A Preliminary Study","volume":"2","author":"Loreto","year":"2013","journal-title":"Open J. Apoptosis"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Amaro, E.R., Ortiz, F.R., Dorneles, L.S., de Souza Santos, M., Barrioni, B.R., Miranda, R.M., Garlet, G.P., Teixeira, M.M., Szawka, R.E., and Silva, T.A. (2020). Estrogen protects dental roots from orthodontic-induced inflammatory resorption. Arch. Oral. Biol., 117.","DOI":"10.1016\/j.archoralbio.2020.104820"},{"key":"ref_66","first-page":"86","article-title":"Optimum force magnitude for orthodontic tooth movement: A systematic literature review","volume":"73","author":"Ren","year":"2003","journal-title":"Angle Orthod."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"e5408","DOI":"10.1590\/pboci.2020.148","article-title":"Hyalinization and Molecular Pathways Involved in Orthodontic Tooth Movement: A Systematic Review and Meta-Analysis","volume":"20","author":"Jamali","year":"2020","journal-title":"Pesqui. Bras. Em Odontopediatria E Cl\u00ednica Integr."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"20190108","DOI":"10.1098\/rsif.2019.0108","article-title":"In vivo effects of different orthodontic loading on root resorption and correlation with mechanobiological stimulus in periodontal ligament","volume":"16","author":"Zhong","year":"2019","journal-title":"J. R. Soc. Interface"},{"key":"ref_69","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_70","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.kjms.2018.01.007","article-title":"Orthodontic tooth movement: The biology and clinical implications","volume":"34","author":"Li","year":"2018","journal-title":"Kaohsiung J. Med. Sci."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1006\/cyto.2001.0974","article-title":"C-reactive protein levels are influenced by common IL-1 gene variations","volume":"17","author":"Berger","year":"2002","journal-title":"Cytokine"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Amezcua-Castillo, E., Gonz\u00e1lez-Pacheco, H., S\u00e1enz-San Mart\u00edn, A., M\u00e9ndez-Ocampo, P., Gutierrez-Moctezuma, I., Mass\u00f3, F., Sierra-Lara, D., Springall, R., Rodr\u00edguez, E., and Arias-Mendoza, A. (2023). C-reactive protein: The quintessential marker of systemic inflammation in coronary artery disease\u2014Advancing toward precision medicine. Biomedicines, 11.","DOI":"10.3390\/biomedicines11092444"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1864","DOI":"10.1177\/00220345000790110801","article-title":"Polymorphisms in the IL-1A gene are correlated with levels of interleukin-1\u03b1 protein in gingival crevicular fluid of teeth with severe periodontal disease","volume":"79","author":"Shirodaria","year":"2000","journal-title":"J. Dent. Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1111\/imr.12620","article-title":"Interleukin 1 gene polymorphism and susceptibility to disease","volume":"281","author":"Khazim","year":"2018","journal-title":"Immunol. Rev."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1111\/j.1600-051X.2007.01086.x","article-title":"Single-nucleotide polymorphisms in the IL-4 and IL-13 promoter region in aggressive periodontitis","volume":"34","author":"Gonzales","year":"2007","journal-title":"J. Clin. Periodontol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1515","DOI":"10.1902\/jop.2006.050427","article-title":"Assessment of single nucleotide polymorphism at IL-1A+ 4845 and IL-1B+ 3954 as genetic susceptibility test for chronic periodontitis in Maharashtrian ethnicity","volume":"77","author":"Agrawal","year":"2006","journal-title":"J. Periodontol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1111\/j.1601-0825.2012.01973.x","article-title":"IL 1 gene polymorphisms in relation to external apical root resorption concurrent with orthodontia","volume":"19","author":"Cernochova","year":"2013","journal-title":"Oral. Dis."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1111\/j.1601-0825.2011.01865.x","article-title":"Postorthodontic external root resorption is associated with IL1 receptor antagonist gene variations","volume":"18","year":"2012","journal-title":"Oral. Dis."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Yu, J., Choi, Y.J., Choi, S.-H., Jung, H.-S., Lee, J.H., and Cha, J.-Y. (2021). The effect of genetic polymorphisms on treatment duration following premolar extraction. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-94979-8"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1093\/ejo\/cjh097","article-title":"Matrix metalloproteinase-1 and-8 in gingival crevicular fluid during orthodontic tooth movement: A pilot study during 1 month of follow-up after fixed appliance activation","volume":"27","author":"Ingman","year":"2005","journal-title":"Eur. J. Orthod."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"e22550","DOI":"10.1096\/fj.202200037R","article-title":"Macrophage-mediated extracellular matrix remodeling after fat grafting in nude mice","volume":"36","author":"Zhang","year":"2022","journal-title":"FASEB J."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"3036","DOI":"10.4049\/jimmunol.1302379","article-title":"IFN-\u03b3 primes macrophage activation by increasing phosphatase and tensin homolog via downregulation of miR-3473b","volume":"193","author":"Wu","year":"2014","journal-title":"J. Immunol."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Binlateh, T., Thammanichanon, P., Rittipakorn, P., Thinsathid, N., and Jitprasertwong, P. (2022). Collagen-Based Biomaterials in Periodontal Regeneration: Current Applications and Future Perspectives of Plant-Based Collagen. Biomimetics, 7.","DOI":"10.3390\/biomimetics7020034"},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Li, M., Lv, J., Yang, Y., Cheng, G., Guo, S., Liu, C., and Ding, Y. (2022). Advances of hydrogel therapy in periodontal regeneration\u2014A materials perspective review. Gels, 8.","DOI":"10.3390\/gels8100624"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1902\/jop.2004.75.8.1068","article-title":"Subantimicrobial dose doxycycline enhances the efficacy of scaling and root planing in chronic periodontitis: A multicenter trial","volume":"75","author":"Preshaw","year":"2004","journal-title":"J. Periodontol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.clinthera.2017.11.011","article-title":"Phase 1b study of the safety, pharmacokinetics, and disease-related outcomes of the matrix metalloproteinase-9 inhibitor andecaliximab in patients with rheumatoid arthritis","volume":"40","author":"Gossage","year":"2018","journal-title":"Clin. Ther."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1139\/cjpp-2015-0019","article-title":"Osteopontin is proteolytically processed by matrix metalloproteinase 9","volume":"93","author":"Lindsey","year":"2015","journal-title":"Can. J. Physiol. Pharmacol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"eaaw6143","DOI":"10.1126\/scitranslmed.aaw6143","article-title":"Osteoclast-mediated bone resorption is controlled by a compensatory network of secreted and membrane-tethered metalloproteinases","volume":"12","author":"Zhu","year":"2020","journal-title":"Sci. Transl. Med."},{"key":"ref_89","first-page":"211","article-title":"The role of nitric oxide in orthodontic tooth movement in rats","volume":"72","author":"Shirazi","year":"2002","journal-title":"Angle Orthod."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1093\/ejo\/cjv071","article-title":"Critical roles of periostin in the process of orthodontic tooth movement","volume":"38","author":"Rangiani","year":"2016","journal-title":"Eur. J. Orthod."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1326","DOI":"10.1089\/ten.tea.2018.0268","article-title":"Periostin and CCN2 scaffolds promote the wound healing response in the skin of diabetic mice","volume":"25","author":"Elliott","year":"2019","journal-title":"Tissue Eng. Part A"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1007\/s00441-016-2426-6","article-title":"Periostin as a multifunctional modulator of the wound healing response","volume":"365","author":"Walker","year":"2016","journal-title":"Cell Tissue Res."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Abdolalian, F., Bayani, M., Afzali, S., Nakhostin, A., and Almasi-Hashiani, A. (2023). Periostin level in gingival crevicular fluid in periodontal disease: A systematic review and meta-analysis. BMC Oral. Health, 23.","DOI":"10.1186\/s12903-023-03031-w"},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Cao, L., Zhang, Z., Yuan, D., Yu, M., and Min, J. (2024). Tissue engineering applications of recombinant human collagen: A review of recent progress. Front. Bioeng. Biotechnol., 12.","DOI":"10.3389\/fbioe.2024.1358246"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"49","DOI":"10.4161\/bioe.26002","article-title":"Human collagen produced in plants: More than just another molecule","volume":"5","author":"Shoseyov","year":"2014","journal-title":"Bioengineered"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1093\/ejo\/cjz027","article-title":"Injectable RANKL sustained release formulations to accelerate orthodontic tooth movement","volume":"42","author":"Chang","year":"2020","journal-title":"Eur. J. Orthod."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1016\/j.actbio.2016.12.006","article-title":"RANKL release from self-assembling nanofiber hydrogels for inducing osteoclastogenesis in vitro","volume":"49","author":"Xing","year":"2017","journal-title":"Acta Biomater."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Thang, N.H., Chien, T.B., and Cuong, D.X. (2023). Polymer-based hydrogels applied in drug delivery: An overview. Gels, 9.","DOI":"10.3390\/gels9070523"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"102191","DOI":"10.1016\/j.scr.2021.102191","article-title":"An induced pluripotent stem cells line (ZZUNEUi022-A) derived from urine cells of healthy male human","volume":"51","author":"Liu","year":"2021","journal-title":"Stem Cell Res."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Chen, I.-P. (2020). Differentiation of human induced pluripotent stem cells (hiPSCs) into osteoclasts. Bio-Protocol, 10.","DOI":"10.21769\/BioProtoc.3854"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1021\/acs.biomac.7b01590","article-title":"pH-responsive microencapsulation systems for the oral delivery of polyanhydride nanoparticles","volume":"19","author":"Sharpe","year":"2018","journal-title":"Biomacromolecules"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1186\/s13287-023-03547-6","article-title":"Comparison of osteoclast differentiation protocols from human induced pluripotent stem cells of different tissue origins","volume":"14","author":"Ijeoma","year":"2023","journal-title":"Stem Cell Res. Ther."},{"key":"ref_103","first-page":"361","article-title":"Effects of human urine-derived stem cells on the cementogenic differentiation of indirectly-cocultured periodontal ligament stem cells","volume":"12","author":"Yang","year":"2020","journal-title":"Am. J. Transl. Res."},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Yang, T., Li, Y., Hong, Y., Chi, L., Liu, C., Lan, Y., Wang, Q., Yu, Y., Xu, Q., and Teng, W. (2020). The construction of biomimetic cementum through a combination of bioskiving and fluorine-containing biomineralization. Front. Bioeng. Biotechnol., 8.","DOI":"10.3389\/fbioe.2020.00341"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"e00217","DOI":"10.1002\/prp2.217","article-title":"In vitro and in vivo drug disposition of cilengitide in animals and human","volume":"4","author":"Dolgos","year":"2016","journal-title":"Pharmacol. Res. Perspect."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"4557","DOI":"10.1080\/21655979.2022.2029236","article-title":"Cilengitide, an \u03b1v\u03b23-integrin inhibitor, enhances the efficacy of anti-programmed cell death-1 therapy in a murine melanoma model","volume":"13","author":"Pan","year":"2022","journal-title":"Bioengineered"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1111\/iej.13715","article-title":"Present status and future directions: Root resorption","volume":"55","author":"Patel","year":"2022","journal-title":"Int. Endod. J."},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Klinder, A., Waletzko-Hellwig, J., Sellin, M.-L., Seyfarth-Sehlke, A., Wolfien, M., Prehn, F., Bader, R., and Jonitz-Heincke, A. (2022). Effects of the Interleukin-6 Receptor Blocker Sarilumab on Metabolic Activity and Differentiation Capacity of Primary Human Osteoblasts. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14071390"},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Steemers, E., Talbi, W.M.I., Hogervorst, J.M.A., Schoenmaker, T., and de Vries, T.J. (2025). IL-1 Receptor Antagonist Anakinra Inhibits the Effect of IL-1\u03b2- Mediated Osteoclast Formation by Periodontal Ligament Fibroblasts. Biology, 14.","DOI":"10.3390\/biology14030250"},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Sincere, N.I., Anand, K., Ashique, S., Yang, J., and You, C. (2023). PROTACs: Emerging targeted protein degradation approaches for advanced druggable strategies. Molecules, 28.","DOI":"10.3390\/molecules28104014"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"8902","DOI":"10.1021\/jacs.1c03852","article-title":"TF-PROTACs enable targeted degradation of transcription factors","volume":"143","author":"Liu","year":"2021","journal-title":"J. Am. Chem. Soc."},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Verzella, D., Cornice, J., Arboretto, P., Vecchiotti, D., Di Vito Nolfi, M., Capece, D., Zazzeroni, F., and Franzoso, G. (2022). The NF-\u03baB pharmacopeia: Novel strategies to subdue an intractable target. Biomedicines, 10.","DOI":"10.3390\/biomedicines10092233"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"7380","DOI":"10.1021\/jacs.1c00451","article-title":"Cancer selective target degradation by folate-caged PROTACs","volume":"143","author":"Liu","year":"2021","journal-title":"J. Am. Chem. Soc."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1306","DOI":"10.1021\/acschembio.0c00285","article-title":"Antibody\u2013PROTAC conjugates enable HER2-dependent targeted protein degradation of BRD4","volume":"15","author":"Maneiro","year":"2020","journal-title":"ACS Chem. Biol."},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Fu, C., Gan, L., Yang, B., Wu, Y., Meng, B., Wu, D., Zheng, J., and Cao, Y. (2022). Inhibitory effect of infliximab on orthodontic tooth movement in male rats. Arch. Oral. Biol., 144.","DOI":"10.1016\/j.archoralbio.2022.105573"},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Perp\u00e9tuo, I.P., Caetano-Lopes, J., Rodrigues, A.M., Campanilho-Marques, R., Ponte, C., Canh\u00e3o, H., Ainola, M., and Fonseca, J.E. (2017). Effect of tumor necrosis factor inhibitor therapy on osteoclasts precursors in rheumatoid arthritis. BioMed Res. Int., 2017.","DOI":"10.1155\/2017\/2690402"},{"key":"ref_117","doi-asserted-by":"crossref","unstructured":"Sarapultsev, A., Gusev, E., Komelkova, M., Utepova, I., Luo, S., and Hu, D. (2023). JAK-STAT signaling in inflammation and stress-related diseases: Implications for therapeutic interventions. Mol. Biomed., 4.","DOI":"10.1186\/s43556-023-00151-1"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12974-015-0334-4","article-title":"Caspase-1 inhibitor ameliorates experimental autoimmune myasthenia gravis by innate dendric cell IL-1-IL-17 pathway","volume":"12","author":"Wang","year":"2015","journal-title":"J. Neuroinflammation"},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Palmroth, M., Kuuliala, K., Peltomaa, R., Virtanen, A., Kuuliala, A., Kurttila, A., Kinnunen, A., Leirisalo-Repo, M., Silvennoinen, O., and Isom\u00e4ki, P. (2021). Tofacitinib suppresses several JAK-STAT pathways in rheumatoid arthritis in vivo and baseline signaling profile associates with treatment response. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.738481"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"12442","DOI":"10.1073\/pnas.1816410116","article-title":"JAK\/STAT inhibition in macrophages promotes therapeutic resistance by inducing expression of protumorigenic factors","volume":"116","author":"Irey","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1186\/s12967-023-04449-0","article-title":"CX3CL1 promotes M1 macrophage polarization and osteoclast differentiation through NF-\u03baB signaling pathway in ankylosing spondylitis in vitro","volume":"21","author":"Feng","year":"2023","journal-title":"J. Transl. Med."},{"key":"ref_122","doi-asserted-by":"crossref","unstructured":"Yordanova, R., Strashimirov, D., Grozdeva, R., Ivanov, D., Trifonova, I., Yancheva, N., and Tcherveniakova, T. (2024). Dynamics of Biomarkers in COVID-19 Patients Treated with Anakinra. Biomedicines, 12.","DOI":"10.20944\/preprints202409.0840.v1"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1186\/s13054-020-03364-w","article-title":"Anakinra treatment in critically ill COVID-19 patients: A prospective cohort study","volume":"24","author":"Kooistra","year":"2020","journal-title":"Crit. Care"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1471-2121-8-4","article-title":"Interleukin-10 inhibits osteoclastogenesis by reducing NFATc1 expression and preventing its translocation to the nucleus","volume":"8","author":"Evans","year":"2007","journal-title":"BMC Cell Biol."},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Ara\u00fajo, A.A.d., Varela, H., Brito, G.A.d.C., Medeiros, C.A.C.X.d., Ara\u00fajo, L.d.S., do Nascimento, J.H.O., and de Ara\u00fajo J\u00fanior, R.F. (2014). Azilsartan increases levels of IL-10, down-regulates MMP-2, MMP-9, RANKL\/RANK, Cathepsin K and up-regulates OPG in an experimental periodontitis model. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0096750"},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Gao, Y., Min, Q., Li, X., Liu, L., Lv, Y., Xu, W., Liu, X., and Wang, H. (2022). Immune system acts on orthodontic tooth movement: Cellular and molecular mechanisms. Biomed. Res. Int., 2022.","DOI":"10.1155\/2022\/9668610"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1038\/s41413-024-00362-4","article-title":"Mapping RANKL-and OPG-expressing cells in bone tissue: The bone surface cells as activators of osteoclastogenesis and promoters of the denosumab rebound effect","volume":"12","author":"Andreasen","year":"2024","journal-title":"Bone Res."},{"key":"ref_128","doi-asserted-by":"crossref","unstructured":"Wu, K., Huang, D., and Huang, X. (2023). The effects of semaphorin 3A in bone and cartilage metabolism: Fundamental mechanism and clinical potential. Front. Cell Dev. Biol., 11.","DOI":"10.3389\/fcell.2023.1321151"},{"key":"ref_129","doi-asserted-by":"crossref","unstructured":"Kamei, H., Ishii, T., and Nishii, Y. (2022). Semaphorin 3A regulates alveolar bone remodeling on orthodontic tooth movement. Sci. Rep., 12.","DOI":"10.1038\/s41598-022-13217-x"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"3813","DOI":"10.1096\/fj.08-106302","article-title":"FHL2 mediates dexamethasone-induced mesenchymal cell differentiation into osteoblasts by activating Wnt\/\u03b2-catenin signaling-dependent Runx2 expression","volume":"22","author":"Hamidouche","year":"2008","journal-title":"FASEB J."},{"key":"ref_131","doi-asserted-by":"crossref","unstructured":"Chang, Y., Park, H., Yang, H.-J., Lee, S., Lee, K.-Y., Kim, T.S., Jung, J., and Shin, J.-M. (2018). Cancer drug response profile scan (CDRscan): A deep learning model that predicts drug effectiveness from cancer genomic signature. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-27214-6"},{"key":"ref_132","doi-asserted-by":"crossref","unstructured":"Nourbakhsh, M., Degn, K., Saksager, A., Tiberti, M., and Papaleo, E. (2024). Prediction of cancer driver genes and mutations: The potential of integrative computational frameworks. Brief. Bioinform., 25.","DOI":"10.1093\/bib\/bbad519"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"148","DOI":"10.3390\/ddc3010009","article-title":"Revolutionizing drug discovery: A comprehensive review of AI applications","volume":"3","author":"Dhudum","year":"2024","journal-title":"Drugs Drug Candidates"},{"key":"ref_134","doi-asserted-by":"crossref","unstructured":"Papavassiliou, K.A., Sofianidi, A.A., Gogou, V.A., and Papavassiliou, A.G. (2024). The Promise of Artificial Intelligence in Reshaping Anticancer Drug Development. Cells, 13.","DOI":"10.3390\/cells13201709"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1038\/s41567-024-02411-5","article-title":"Drug design on quantum computers","volume":"20","author":"Santagati","year":"2024","journal-title":"Nat. Phys."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1038\/s43018-024-00756-7","article-title":"PERCEPTION predicts patient response and resistance to treatment using single-cell transcriptomics of their tumors","volume":"5","author":"Sinha","year":"2024","journal-title":"Nat. Cancer"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1111\/ocr.12493","article-title":"Accuracy of automated identification of lateral cephalometric landmarks using cascade convolutional neural networks on lateral cephalograms from nationwide multi-centres","volume":"24","author":"Kim","year":"2021","journal-title":"Orthod. Craniofacial Res."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"4299","DOI":"10.1007\/s00784-021-03990-w","article-title":"Deep learning for cephalometric landmark detection: Systematic review and meta-analysis","volume":"25","author":"Schwendicke","year":"2021","journal-title":"Clin. Oral. Investig."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"102028","DOI":"10.1016\/j.media.2021.102028","article-title":"Cephalogram synthesis and landmark detection in dental cone-beam CT systems","volume":"70","author":"Huang","year":"2021","journal-title":"Med. Image Anal."},{"key":"ref_140","doi-asserted-by":"crossref","unstructured":"Adel, S.M., Vaid, N.R., El-Harouni, N., Kassem, H., and Zaher, A.R. (2022). Digital model superimpositions: Are different software algorithms equally accurate in quantifying linear tooth movements?. BMC Oral. Health, 22.","DOI":"10.1186\/s12903-022-02129-x"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1007\/s00784-023-05440-1","article-title":"Deep learning for virtual orthodontic bracket removal: Tool establishment and application","volume":"28","author":"Li","year":"2024","journal-title":"Clin. Oral. Investig."},{"key":"ref_142","doi-asserted-by":"crossref","unstructured":"Park, J.H., Hamimi, M., Choi, J.J.E., Figueredo, C.M.S., and Cameron, M.A. (2025). Comparisons of AI automated segmentation techniques to manual segmentation techniques of the maxilla and maxillary sinus for CT or CBCT scans\u2014A Systematic review. Dentomaxillofacial Radiol., twaf042.","DOI":"10.1093\/dmfr\/twaf042"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1007\/s00784-025-06183-x","article-title":"Automatic multimodal registration of cone-beam computed tomography and intraoral scans: A systematic review and meta-analysis","volume":"29","author":"Zheng","year":"2025","journal-title":"Clin. Oral. Investig."},{"key":"ref_144","doi-asserted-by":"crossref","unstructured":"Bichu, Y.M., Zou, B., Chaudhari, P.K., Adel, S.M., and Vaiid, N. (2025). Artificial Intelligence Applications in Orthodontics. Artificial Intelligence for Oral Health Care: Applications and Future Prospects, Springer.","DOI":"10.1007\/978-3-031-84047-0_6"},{"key":"ref_145","doi-asserted-by":"crossref","unstructured":"Reduwan, N.H., Aziz, A.A., Mohd Razi, R., Abdullah, E.R.M.F., Mazloom Nezhad, S.M., Gohain, M., and Ibrahim, N. (2024). Application of deep learning and feature selection technique on external root resorption identification on CBCT images. BMC Oral. Health, 24.","DOI":"10.1186\/s12903-024-03910-w"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"6893","DOI":"10.1007\/s00784-022-04742-0","article-title":"Accuracy of artificial intelligence for tooth extraction decision-making in orthodontics: A systematic review and meta-analysis","volume":"26","author":"Evangelista","year":"2022","journal-title":"Clin. Oral. Investig."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"158","DOI":"10.4103\/aihb.aihb_140_24","article-title":"The Use of Artificial Intelligence in Orthodontic Treatment Planning: A Systematic Review and Meta-analysis","volume":"15","author":"Ingle","year":"2025","journal-title":"Adv. Hum. Biol."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1177\/00220345241235606","article-title":"Artificial intelligence in orthodontics: Critical review","volume":"103","author":"Nordblom","year":"2024","journal-title":"J. Dent. Res."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1007\/s00784-024-05781-5","article-title":"Insights into predicting tooth extraction from panoramic dental images: Artificial intelligence vs. dentists","volume":"28","author":"Motmaen","year":"2024","journal-title":"Clin. Oral. Investig."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1016\/j.prosdent.2021.07.010","article-title":"Measuring tooth movement with treatment using the Dahl principle: An observational study","volume":"129","author":"Bhai","year":"2023","journal-title":"J. Prosthet. Dent."},{"key":"ref_151","doi-asserted-by":"crossref","unstructured":"Kazimierczak, N., Kazimierczak, W., Serafin, Z., Nowicki, P., No\u017cewski, J., and Janiszewska-Olszowska, J. (2024). AI in Orthodontics: Revolutionizing Diagnostics and Treatment Planning\u2014A Comprehensive Review. J. Clin. Med., 13.","DOI":"10.3390\/jcm13020344"},{"key":"ref_152","doi-asserted-by":"crossref","unstructured":"Liu, J., Zhang, C., and Shan, Z. (2023). Application of artificial intelligence in orthodontics: Current state and future perspectives. Healthcare, 11.","DOI":"10.3390\/healthcare11202760"},{"key":"ref_153","first-page":"E160","article-title":"Correction to Lancet Digital Health 2019; 1: e106\u201307","volume":"1","author":"Lou","year":"2019","journal-title":"Corrections"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1038\/s41392-024-01809-0","article-title":"Induced pluripotent stem cells (iPSCs): Molecular mechanisms of induction and applications","volume":"9","author":"Cerneckis","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_155","doi-asserted-by":"crossref","unstructured":"Montero Jim\u00e9nez, O.G., Dib Kan\u00e1n, A., Dipp Vel\u00e1zquez, F.A., Aristiz\u00e1bal P\u00e9rez, J.F., Moyaho Bernal, M.d.l.\u00c1., Salas Orozco, M.F., and Casillas Santana, M.A. (2022). Use of hydrogels to regulate orthodontic tooth movement in animal models: A systematic review. Appl. Sci., 12.","DOI":"10.3390\/app12136683"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.actbio.2021.11.011","article-title":"Hydroxyapatite-decorated Fmoc-hydrogel as a bone-mimicking substrate for osteoclast differentiation and culture","volume":"138","author":"Vitale","year":"2022","journal-title":"Acta Biomater."},{"key":"ref_157","doi-asserted-by":"crossref","unstructured":"Anjum, S., Wang, Y., Xin, Y., Li, X., Li, T., Zhang, H., Quan, L., Li, Y., Arya, D.K., and Rajinikanth, P. (2024). Bioinspired core-shell nanofiber drug-delivery system modulates osteogenic and osteoclast activity for bone tissue regeneration. Mater. Today Bio, 26.","DOI":"10.1016\/j.mtbio.2024.101088"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1007\/s40820-024-01536-9","article-title":"Unleashing the potential of electroactive hybrid biomaterials and self-powered systems for bone therapeutics","volume":"17","author":"Liu","year":"2025","journal-title":"Nano-Micro Lett."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"4375","DOI":"10.1016\/S0142-9612(03)00337-5","article-title":"Controlled release by biodegradable hydrogels enhances the ectopic bone formation of bone morphogenetic protein","volume":"24","author":"Yamamoto","year":"2003","journal-title":"Biomaterials"},{"key":"ref_160","doi-asserted-by":"crossref","unstructured":"Jeong, J., and Kim, J. (2021). Cyclic RGD pentapeptide cilengitide enhances efficacy of gefitinib on TGF-\u03b21-induced epithelial-to-mesenchymal transition and invasion in human non-small cell lung cancer cells. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.639095"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"2438","DOI":"10.1021\/acs.jmedchem.3c01414","article-title":"Discovery of Novel Potent and Fast BTK PROTACs for the Treatment of Osteoclasts-Related Inflammatory Diseases","volume":"67","author":"Huang","year":"2024","journal-title":"J. Med. Chem."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"6711","DOI":"10.3892\/mmr.2015.4328","article-title":"Effects of intermedin on proliferation, apoptosis and the expression of OPG\/RANKL\/M-CSF in the MC3T3-E1 osteoblast cell line","volume":"12","author":"Ren","year":"2015","journal-title":"Mol. Med. Rep."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1016\/j.jbusres.2020.09.068","article-title":"Augmenting organizational decision-making with deep learning algorithms: Principles, promises, and challenges","volume":"123","author":"Shrestha","year":"2021","journal-title":"J. Bus. Res."},{"key":"ref_164","doi-asserted-by":"crossref","unstructured":"Li, Y.-H., Li, Y.-L., Wei, M.-Y., and Li, G.-Y. (2024). Innovation and challenges of artificial intelligence technology in personalized healthcare. Sci. Rep., 14.","DOI":"10.1038\/s41598-024-70073-7"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"1730","DOI":"10.1056\/NEJMhpr063086","article-title":"FDA regulation of stem-cell-based therapies","volume":"355","author":"Halme","year":"2006","journal-title":"N. Engl. J. Med."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/17\/8203\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:34:52Z","timestamp":1760034892000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/17\/8203"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,23]]},"references-count":165,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["ijms26178203"],"URL":"https:\/\/doi.org\/10.3390\/ijms26178203","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,23]]}}}