F4/80 inhibits osteoclast differentiation via downregulation of nuclear factor of activated T cells, cytoplasmic 1

• Published in: Archives of pharmacal research Vol. 40; no. 4; pp. 492 - 499
• Main Authors: Kang, Ju-Hee, Sim, Jung-Sun, Zheng, Ting, Yim, Mijung
• Format: Journal Article
• Language: English
• Published: Seoul Pharmaceutical Society of Korea 01.04.2017; 대한약학회
• Subjects: Animals; bone metabolism; Cell Differentiation - drug effects; Cells, Cultured; cyclic AMP; Down-Regulation - drug effects; gene expression; glycoproteins; Glycoproteins - metabolism; interferon-beta; macrophages; Medicine; messenger RNA; Mice; Mice, Inbred C57BL; NFATC Transcription Factors - antagonists & inhibitors; NFATC Transcription Factors - metabolism; osteoclasts; Osteoclasts - cytology; Osteoclasts - drug effects; Pharmacology/Toxicology; Pharmacy; phosphorylation; Research Article; T-lymphocytes; 약학; RANKL; Osteoclast; NFATc1; F4/80; Bone loss
• ISSN: 0253-6269; 1976-3786; 1976-3786
• DOI: 10.1007/s12272-017-0900-7

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-β, 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-β. Therefore, F4/80 may hold therapeutic potential for bone destructive diseases.