TRAP-positive osteoclast precursors mediate ROS/NO-dependent bactericidal activity via TLR4

Kazuaki Nishimura, Satoru Shindo, Alexandru Movila, Rayyan Kayal, Albassam Abdullah, Irma Josefina Savitri, Atsushi Ikeda, Tsuguno Yamaguchi, Mohammed Howait, Ayman Al-dharrab, Abdulghani Mira, Xiaozhe Han, Toshihisa Kawai

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)


Osteoclastogenesis was induced by RANKL stimulation in mouse monocytes to examine the possible bactericidal function of osteoclast precursors (OCp) and mature osteoclasts (OCm) relative to their production of NO and ROS. Tartrate-resistant acid phosphatase (TRAP)-positive OCp, but few or no OCm, phagocytized and killed Escherichia coli in association with the production of reactive oxygen species (ROS) and nitric oxide (NO). Phagocytosis of E. coli and production of ROS and NO were significantly lower in TRAP+ OCp derived from Toll-like receptor (TLR)-4 KO mice than that derived from wild-type (WT) or TLR2-KO mice. Interestingly, after phagocytosis, TRAP+ OCp derived from wild-type and TLR2-KO mice did not differentiate into OCm, even with continuous exposure to RANKL. In contrast, E. coli-phagocytized TRAP+ OCp from TLR4-KO mice could differentiate into OCm. Importantly, neither NO nor ROS produced by TRAP+ OCp appeared to be engaged in phagocytosis-induced suppression of osteoclastogenesis. These results suggested that TLR4 signaling not only induces ROS and NO production to kill phagocytized bacteria, but also interrupts OCm differentiation. Thus, it can be concluded that TRAP+ OCp, but not OCm, can mediate bactericidal activity via phagocytosis accompanied by the production of ROS and NO via TLR4-associated reprograming toward phagocytic cell type.

Original languageEnglish
Pages (from-to)330-341
Number of pages12
JournalFree Radical Biology and Medicine
Publication statusPublished - 1 Aug 2016


  • Bacteria
  • Nitric oxide
  • Osteoclast
  • Phagocytosis
  • Reactive oxygen species
  • Tartrate-resistant acid phosphatase
  • Toll-like receptor


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