HMGB1-induced inflammatory response promotes bone healing in murine tooth extraction socket

Hiroaki Aoyagi, Keisuke Yamashiro, Chiaki Hirata-Yoshihara, Hidetaka Ideguchi, Mutsuyo Yamasaki, Mari Kawamura, Tadashi Yamamoto, Shinsuke Kochi, Hidenori Wake, Masahiro Nishibori, Shogo Takashiba

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)


High mobility group box 1 (HMGB1) is a non-histone DNA-binding protein that is secreted into the extracellular milieu in response to inflammatory stimuli. The secreted HMGB1 has been suggested to mediate various inflammatory diseases. However, it is still unknown whether HMGB1 is involved in a healing process in the tooth extraction socket, the tissue containing gingival epithelium, and alveolar bone that is exposed to oral bacteria. In this study, we constructed a murine tooth extraction model with anti-HMGB1 neutralization antibody administration and observed the inflammatory response and bone healing process in tooth extraction sockets by molecular imaging of myeloperoxidase (MPO) activity, histological analysis, and quantitative RT-PCR. The translocation of HMGB1 from the nucleus to the cytoplasm in gingival epithelial cells and inflammatory cells was inhibited by anti-HMGB1 antibody administration. The MPO activity around the tooth extraction socket was significantly reduced, and the numbers of CD31- and CD68-positive cells were significantly lower in the anti-HMGB1 antibody treatment samples than in the control samples. The TRAP-positive cells, osteocalcin positive cells, and the neoplastic bone area were significantly lower in anti-HMGB1 antibody treatment samples than in control samples. The expression levels of IL-1β and VEGF-A were also decreased in anti-HMGB1 antibody treatment samples compared to that in control samples. Secreted HMGB1 induced initial acute inflammation and inflammatory cells recruitment after tooth extraction. HMGB1 was associated with angiogenesis and bone remodeling by osteoclast and osteoblast activation and promoted bone healing in the tooth extraction socket.

Original languageEnglish
Pages (from-to)5481-5490
Number of pages10
JournalJournal of Cellular Biochemistry
Issue number7
Publication statusPublished - Jul 2018


  • HMGB1
  • angiogenesis
  • bone healing
  • inflammation
  • tooth extraction

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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