{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T19:26:58Z","timestamp":1787081218958,"version":"build-2736575974"},"reference-count":32,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T00:00:00Z","timestamp":1771372800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T00:00:00Z","timestamp":1771372800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["No.82471022,82471019and82301090"],"award-info":[{"award-number":["No.82471022,82471019and82301090"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Orthod Craniofacial Res"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>In this exploratory pilot study, we profiled human periodontal ligament (PDL) transcriptomes during early orthodontic tooth movement (OTM). Early\u2010stage (0\u201310\u2009days) transcriptional dynamics under tension and compression remain insufficiently understood, and no dedicated user\u2010friendly resource has been available for exploring large\u2010scale human data.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We established tooth extrusion and intrusion models to simulate tension\u2010 and compression\u2010side PDL conditions, respectively, and collected human PDL samples within the first 10\u2009days (days 0, 1, 3 and 10; \u2264 4 biological replicates per force\u2013time subgroup). RNA\u2010seq was performed, and five complementary gene selection strategies identified persistent force\u2010specific genes, time\u2010dependent concurrent genes, force\u2010dominant genes, condition\u2010specific markers and integrative network modules. We also developed a Shiny\u2010based web application (HOTM) to integrate the processed data, enabling OTM\u2010related analyses\u2014such as custom comparisons, expression visualisation and correlation assessments\u2014in a simple, code\u2010free environment. Given the pilot design, candidate genes were prioritised using nominal P\u2010values for exploratory screening; multiple\u2010testing\u2013adjusted statistics are provided for reference in the supplementary results and HOTM.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Persistent extrusion\u2010upregulated genes (CAR1, ACTB) were consistent with a proliferation\u2010associated program under tension, whereas persistent intrusion\u2010upregulated genes (CXCR6, CCL5) were consistent with immunomodulatory signatures under compression. Concurrently upregulated genes showed a time\u2010related transition from early immune activation (CD28, day 1) to proliferation (MYC, day 3) and metabolic specialisation (GAPDH, day 10). Extrusion\u2010dominant genes (BYSL) suggested controlled growth and metabolic stability, while intrusion\u2010dominant genes (CLDN7) were associated with an osteoclast\u2010favouring remodelling signature. Condition\u2010specific markers suggested a time\u2010dependent progression from early immunoinflammatory cues to advanced tissue reorganisation. Integrative modules pointed to candidate hub genes linking extrusion\u2010associated proliferation (SHCBP1, BIRC5, ARHGAP11A) and intrusion\u2010associated remodelling (ATP6V1A, ATP6V1B2, SNX10) to a core metabolic and protein homeostasis baseline (MRPL47, PSMC2, UBE2V2).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This exploratory pilot study presents a hypothesis\u2010generating transcriptomic resource describing early (0\u201310\u2009day) human PDL responses to orthodontic extrusion and intrusion and a publicly accessible web tool (HOTM) for convenient exploration of candidate genes and pathways. All findings should be interpreted as exploratory and require confirmation in independent, adequately powered cohorts with appropriate multiple\u2010testing correction and orthogonal validation before mechanistic or clinical interpretation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/ocr.70103","type":"journal-article","created":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T18:34:12Z","timestamp":1771439652000},"page":"611-623","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Human Periodontal Ligament Transcriptomes Under Orthodontic Extrusion and Intrusion: An Exploratory Pilot\n                    <scp>RNA<\/scp>\n                    \u2010Seq Study With an Interactive Public Web Tool"],"prefix":"10.1111","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0707-0928","authenticated-orcid":false,"given":"Xiaoqi","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Orthodontics, State Key Laboratory of Oral Diseases, National Clinical Research Center of Oral Diseases West China Hospital of Stomatology, Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Xing","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, State Key Laboratory of Oral Diseases, National Clinical Research Center of Oral Diseases West China Hospital of Stomatology, Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7873-9516","authenticated-orcid":false,"given":"Waseem","family":"AI\u2010Gumaei","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, State Key Laboratory of Oral Diseases, National Clinical Research Center of Oral Diseases West China Hospital of Stomatology, Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4056-0080","authenticated-orcid":false,"given":"Xiaoqian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Yunnan Key Laboratory of Stomatology Affiliated Hospital of Stomatology School of Stomatology Kunming Medical University  Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingxuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, State Key Laboratory of Oral Diseases, National Clinical Research Center of Oral Diseases West China Hospital of Stomatology, Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minqi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Bone Metabolism, School and Hospital of Stomatology, Cheeloo College of Medicine Shandong University  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6020-6559","authenticated-orcid":false,"given":"Hu","family":"Long","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, State Key Laboratory of Oral Diseases, National Clinical Research Center of Oral Diseases West China Hospital of Stomatology, Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7652-739X","authenticated-orcid":false,"given":"Wenli","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, State Key Laboratory of Oral Diseases, National Clinical Research Center of Oral Diseases West China Hospital of Stomatology, Sichuan University  Chengdu 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