F4/80 inhibits osteoclast differentiation via downregulation of nuclear factor of activated T cells, cytoplasmic 1
- Authors
- Kang, Ju-Hee; Sim, Jung-Sun; Zheng, Ting; Yim, Mijung
- Issue Date
- Apr-2017
- Publisher
- PHARMACEUTICAL SOC KOREA
- Keywords
- F4/80; Osteoclast; RANKL; NFATc1; Bone loss
- Citation
- ARCHIVES OF PHARMACAL RESEARCH, v.40, no.4, pp 492 - 499
- Pages
- 8
- Journal Title
- ARCHIVES OF PHARMACAL RESEARCH
- Volume
- 40
- Number
- 4
- Start Page
- 492
- End Page
- 499
- URI
- https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/8584
- DOI
- 10.1007/s12272-017-0900-7
- ISSN
- 0253-6269
1976-3786
- Abstract
- 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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