Jaw-specific differential kinase activity profiles in human periodontal ligament stem cells under mechanical compression

  • Christian Niederau*
  • , Sanne L. Maas
  • , Emiel P. C. van der Vorst
  • , Leon J. Schurgers
  • , Yang Shi
  • , Frank Holzle
  • , Michael Wolf
  • , Rogerio B. Craveiro
  • *Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

BackgroundIncreasing clinical and experimental evidence suggests that the upper and lower jaw exhibit pronounced functional and structural disparities that cannot be explained solely by classical anatomical differences. A central, yet unresolved question is whether periodontal ligament stem cells (PDLSCs) from these distinct regions display site-specific molecular signaling patterns in response to mechanical stress. We propose that PDLSCs derived from maxillary and mandibular regions activate distinct kinase signaling networks upon mechanical stimulation, thereby establishing a jaw-specific mechanobiological fingerprint.MethodsPDLSCs were isolated from seven healthy donor teeth and exposed to a static compressive force of 2 g/cm2. Kinase activity was profiled using a high-throughput PamChip (R) peptide arrays that target both protein tyrosine kinases (PTKs) and serine/threonine kinases (STKs). Downstream pathway enrichment analyses were conducted using the Wikipathways, Gene Ontology (GO), KEGG, and Enriched pathways databases.ResultsMechanical stimulation induced distinct kinase activation signatures depending on jaw origin. Maxillary PDLSCs displayed a predominance of STK activation, while mandibular cells showed a relative reduction in PTK signaling. Only two PTKs and four STKs were consistently regulated across both regions, supporting the presence of a region-specific mechanotransduction profile.ConclusionThese findings support our hypothesis that localized differences in kinase signaling may constitute a molecular basis for the clinically observed jaw-specific phenomena, such as heterogeneous orthodontic tooth movement and alveolar bone remodeling. Jaw-dependent mechanotransduction pathways can therefore be considered key determinants of periodontal biology and may provide a basis for follow-up studies aimed at enabling the development of personalized orthodontic and regenerative strategies.
Original languageEnglish
Article number624
Number of pages17
JournalStem Cell Research & Therapy
Volume16
Issue number1
DOIs
Publication statusPublished - 7 Nov 2025

Keywords

  • Upper jaw
  • Lower jaw
  • Kinase activity
  • Kinomics
  • PamGene
  • Human PDL
  • PDLSC
  • hPdlF
  • Tooth movement
  • Maxilla
  • Mandible
  • R/BIOCONDUCTOR PACKAGE
  • TOOTH MOVEMENT
  • MAXILLA
  • STRESS

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