American journal of orthodontics and dentofacial orthopedics : official publication of the American Association of Orthodontists, its constituent societies, and the American Board of Orthodontics ·6 Nov 2026 ·Added 10 Nov 2026

S100A7 promotes orthodontic tooth movement by enhancing osteoclastogenesis via the receptor for advanced glycation end products.

Shengnan Wu, Xueyu Sun, Hao Xu, Fan Yang, Hanwen Zhang, Bin Yan

Other & Emerging Fields

DOI ↗

Abstract

Orthodontic tooth movement (OTM) requires coordinated remodeling of the periodontal ligament (PDL) and alveolar bone, but clinically relevant molecular regulators remain incompletely defined. We investigated damage-associated molecular patterns (DAMPs) in human PDL and the mechanism by which a candidate DAMP regulates OTM. PDL from premolars exposed or not exposed to 7 days of orthodontic force underwent tandem mass tag-based proteomics. Candidate expression was validated by enzyme-linked immunosorbent assay, reverse transcription-polymerase chain reaction, and immunohistochemistry. Wild-type and mS100a7a15-knockout mouse OTM models, local mS100a7a15 administration, and primary murine osteoclast assays were used to assess function and mechanism. S100A7 was upregulated in force-loaded human PDL and peaked at day 7; its murine homolog, mS100a7a15, showed a similar pattern and was enriched on the compression side. mS100a7a15 deficiency reduced osteoclastogenesis, alveolar bone resorption, and OTM. Recombinant mS100a7a15 enhanced receptor activator of nuclear factor κB (NF-κB) ligand-induced osteoclast differentiation, ubiquitin-conjugating enzyme E2 N (UBE2N) expression, tumor necrosis factor receptor-associated factor 6 (TRAF6) ubiquitination, and NF-κB activation. Receptor for advanced glycation end products antagonism attenuated NF-κB activation and osteoclastogenesis, whereas Ube2n knockdown reduced TRAF6 ubiquitination and osteoclast differentiation. Local mS100a7a15 administration accelerated OTM without further reducing distal alveolar bone height in the 7-day model. S100A7 promotes osteoclast-mediated OTM through the receptor for advanced glycation end products, UBE2N, TRAF6, and NF-κB axis. This pathway may provide a target for modulating orthodontic treatment rate, although long-term periodontal and root safety requires evaluation.