ArticleOrthodontics & craniofacial research2026
Human Periodontal Ligament Transcriptomes Under Orthodontic Extrusion and Intrusion: An Exploratory Pilot RNA-Seq Study With an Interactive Public Web Tool.
Article in Orthodontics & craniofacial research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundIn this exploratory pilot study, we profiled human periodontal ligament (PDL) transcriptomes during early orthodontic tooth movement (OTM). Early-stage (0-10 days) transcriptional dynamics under tension and compression remain insufficiently understood, and no dedicated user-friendly resource has been available for exploring large-scale human data.
methodsWe established tooth extrusion and intrusion models to simulate tension- and compression-side PDL conditions, respectively, and collected human PDL samples within the first 10 days (days 0, 1, 3 and 10; ≤ 4 biological replicates per force-time subgroup). RNA-seq was performed, and five complementary gene selection strategies identified persistent force-specific genes, time-dependent concurrent genes, force-dominant genes, condition-specific markers and integrative network modules. We also developed a Shiny-based web application (HOTM) to integrate the processed data, enabling OTM-related analyses-such as custom comparisons, expression visualisation and correlation assessments-in a simple, code-free environment. Given the pilot design, candidate genes were prioritised using nominal P-values for exploratory screening; multiple-testing-adjusted statistics are provided for reference in the supplementary results and HOTM.
resultsPersistent extrusion-upregulated genes (CAR1, ACTB) were consistent with a proliferation-associated program under tension, whereas persistent intrusion-upregulated genes (CXCR6, CCL5) were consistent with immunomodulatory signatures under compression. Concurrently upregulated genes showed a time-related transition from early immune activation (CD28, day 1) to proliferation (MYC, day 3) and metabolic specialisation (GAPDH, day 10). Extrusion-dominant genes (BYSL) suggested controlled growth and metabolic stability, while intrusion-dominant genes (CLDN7) were associated with an osteoclast-favouring remodelling signature. Condition-specific markers suggested a time-dependent progression from early immunoinflammatory cues to advanced tissue reorganisation. Integrative modules pointed to candidate hub genes linking extrusion-associated proliferation (SHCBP1, BIRC5, ARHGAP11A) and intrusion-associated remodelling (ATP6V1A, ATP6V1B2, SNX10) to a core metabolic and protein homeostasis baseline (MRPL47, PSMC2, UBE2V2).
conclusionsThis exploratory pilot study presents a hypothesis-generating transcriptomic resource describing early (0-10 day) 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-testing correction and orthogonal validation before mechanistic or clinical interpretation.
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