期刊
ARCHIVES OF PHARMACAL RESEARCH
卷 40, 期 4, 页码 492-499出版社
PHARMACEUTICAL SOC KOREA
DOI: 10.1007/s12272-017-0900-7
关键词
F4/80; Osteoclast; RANKL; NFATc1; Bone loss
资金
- Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea [HI14C24470000]
- National Research Foundation of Korea (NRF) - Ministry of Science, ICT and Future Planning (MSIP) [NRF-2014M1A3A3A02034917]
- National Research Foundation of Korea [2014M1A3A3A02034917] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Osteoclastogenesis is an essential process in bone metabolism, which can be induced by RANKL stimulation. The F4/80 glycoprotein is a member of the EGF-transmembrane 7 (TM7) family and has been established as a specific cell-surface marker for murine macrophages. This study aimed to identify the role of F4/80 in osteoclastogenesis. Using mouse bone marrow-derived macrophages (BMMs), we observed that the mRNA level of F4/80 was dramatically reduced as these cells differentiated into osteoclasts. Furthermore, osteoclastogenesis was decreased in F4/80(high) BMMs compared to F4/80(-/low) BMMs. The inhibitory effect of F4/80 was associated with decreased expression of nuclear factor of activated T cells, cytoplasmic 1 (NFATc1). Ectopic overexpression of a constitutively active form of NFATc1 rescued the anti-osteoclastogenic effect of F4/80 completely, suggesting that the anti-osteoclastogenic effect of F4/80 was mainly due to reduction in NFATc1 expression. As an underlying mechanism, we demonstrated that the presence of F4/80 abrogated the effect of RANKL on the phosphorylation of CREB and activated the expression of IFN-beta, which are restored by cyclic AMP. Collectively, our results demonstrate that the presence of F4/80 suppresses RANKL-induced osteoclastogenesis by impairing the expression of NFATc1 via CREB and IFN-beta. Therefore, F4/80 may hold therapeutic potential for bone destructive diseases.
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