Lactoferrin inhibits infection-related osteoclastogenesis without interrupting compressive force-related osteoclastogenesis

T. Inubushi, A. Kawazoe, M. Miyauchi, S. Yanagisawa, A. Subarnbhesaj, C. Chanbora, N. F. Ayuningtyas, A. Ishikado, E. Tanaka, T. Takata

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9 Citations (Scopus)


Background Control of periodontal tissue inflammation during orthodontic treatment is very important in achieving a favourable therapeutic goal. We previously demonstrated that orally applied bovine lactoferrin (bLF) inhibited LPS-induced bone resorption but not orthodontic force-induced tooth movement in vivo. This study is designed to examine the underlying mechanism of it. Methods We examined the inhibitory effects of bLF on the expression of RANKL, OPG, TNF-α and COX-2 in osteoblasts loaded with compressive stress (CS) in comparison with LPS stimulated osteoblasts. Formation of osteoclasts was evaluated by co-culture system. Results Both CS- and LPS-applications upregulated COX-2 and RANKL but downregulated OPG. TNF-α was upregulated in LPS-stimulated osteoblasts but downregulated in CS-loaded osteoblasts. NS398 (a specific inhibitor of COX-2) significantly inhibited CS-induced RANKL-upregulation but not LPS-induced RANKL upregulation, indicating a critical role of COX-2/PGE2 pathway in CS-induced osteoclastogenesis. bLF significantly downregulated LPS-induced upregulation of RANKL and eliminated OPG suppression but not affected in CS-induced changes. Moreover, bLF significantly decreased LPS-induced osteoclast formation, whereas bLF had no effect on PGE2-induced osteoclast formation. Conclusions bLF can effectively suppress harmful bone destruction associated with periodontitis without inhibiting bone remodelling by CS-loading. Therefore, oral administration of bLF may be highly beneficial for control of periodontitis in orthodontic patients.

Original languageEnglish
Pages (from-to)226-232
Number of pages7
JournalArchives of Oral Biology
Issue number2
Publication statusPublished - Feb 2014
Externally publishedYes


  • Anti-inflammatory agents
  • Bone biology
  • Cytokine(s)
  • Lactoferrin
  • Osteoblast(s)
  • Periodontitis


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