期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 389, 期 1, 页码 28-33出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2009.08.080
关键词
CpG-ODN; Osteoclastogenesis; TLR9; TREM-2; NFATc1
资金
- 21C Frontier Functional Proteomics Project [FPR08B1-170]
- Science Research Center [R11-2008-023-01001-0]
- National R&D Program for Cancer Control
- Ministry for Health, Welfare and Family affairs, Republic of Korea [0920020]
- MEST [KRF-2007-359-E00001]
- Korea Health Promotion Institute [0920020] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Recognition of oligodeoxynucleotides containing CpG motifs (CpG-ODNs) by toll-like receptor 9 (TLR9) inhibits RANKL-induced osteoclastogenesis from precursors. This inhibitory effect suggests the possibility of using this strategy to block pathological bone loss. However, the enhancing effect of CpG-ODNs on OC formation from RANKL-primed pre-osteoclasts (pOCs) has hampered their clinical use. In this report, we developed a CpG-KSK13 oligonucleotide with an alternative CpG motif, and tested its effect on osteoclastogenesis in comparison with previously used murine CpG motif (CpG-1826) or human CpG motif (CpG-2006) oligonucleotides. Murine CpG-1826 inhibited RANKL-induced OC formation from BMMs but not from RANKL-primed pOCs, while CpG-KSK13 treatment strongly inhibited OC formation from both BMM and primed pOC cells. CpG-KSK13 also showed a potent inhibitory effect on human OC differentiation using peripheral blood mononuclear cells (PBMCs), which was in contrast to the species-specific response of murine CpG-1826 or human CpG-2006. Moreover, CpG-KSK13 effectively inhibited NFATc1 activity, but not NF-kappa B or AP-1 activity, and decreased TREM-2 promoter activity and subsequent surface expression of the TREM-2 protein induced by M-CSF and RANKL. These results demonstrate that the recognition of CpG-KSK13 via TLR9 inhibits osteoclastogenesis by down-regulating TREM-2 expression. Thus, our findings provide evidence for the potential use of CpG-KSK13 as an anti-osteoclastogenic agent for human and for pre-clinical animals. (C) 2009 Elsevier Inc. All rights reserved.
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