Damage Signal or Regenerative Cue? Unraveling the Biphasic Paradox of High Mobility Group Box-1 in Periodontal Tissues – A Scoping Review
Year: 2026
Type: article
Study design: Systematic Review
Abstract: A BSTRACT Background and Aims: High Mobility Group Box-1 (HMGB1) has emerged as a key mediator in inflammation and tissue remodeling. The goal of this scoping review is to comprehensively outline and evaluate the current literature evidence on HMGB1 in periodontitis, with a focus on its mechanistic role in disease pathogenesis and potential contribution to periodontal repair and regeneration. Guidelines and Sources of Evidence: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Extension for Scoping Reviews guidelines were followed. Literature search was done in PubMed/Medline, Scopus, Cochrane Library, Web of Science, Mendeley, and Google scholar using a blend of MeSH terms, keywords, and non-indexed terms related to “HMGB1,” “periodontitis,” “regeneration,” and “repair.” In addition, a thorough search of bibliographies and gray literature was conducted to ensure comprehensive coverage until August 2025. Results: In total, 362 records were collected initially, duplicates were eliminated, thereafter the titles and abstracts were appraised for relevance, and finally 39 studies were eligible and were retained for detailed analysis. The articles were categorized into those examining HMGB1 as an inflammatory marker ( n = 20), a reparative or regenerative marker ( n = 8), and as a component of inflammatory cytokines or damage-associated molecular patterns (DAMPs) repertoire within periodontal tissues ( n = 11). Conclusions: HMGB1 acts as a DAMP, pro-inflammatory, and osteoclastogenic cytokine, inducing and amplifying inflammation in periodontitis. However, data substantiating its definitive role in periodontal regeneration and repair remain limited and inconclusive. Furthermore, limited studies have elucidated the specific molecular pathways underlying HMGB1 receptor binding, activation pathways, and downstream signaling, highlighting the need for future investigations in this largely unexplored domain.
Institution: SRM Dental College
Language: English
Subfield: Periodontics
Field: Dentistry
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W7204468430