Inhibitory effects of tert‐butylhydroquinone on osteoclast differentiation via up‐regulation of heme oxygenase‐1 and down‐regulation of HMGB1 release and NFATc1 expression. Issue 1 (30th October 2012)

• Record Type: Journal Article
• Authors: Yamaguchi, Yu; Sakai, Eiko; Sakamoto, Hiroshi; Fumimoto, Reiko; Fukuma, Yutaka; Nishishita, Kazuhisa; Okamoto, Kuniaki; Tsukuba, Takayuki
• Is Part Of: Journal of applied toxicology. Volume 34:Issue 1(2014)
• Page Start: 49
• Page End: 56
• Publication Date: 2012-10-30
• Subjects: osteoclasts -- tert‐butylhydroquinone -- heme oxygenase‐1 -- high mobility group box 1 -- nuclear factor of activated T cells cytoplasmic‐1; Toxicology -- Periodicals; Industrial toxicology -- Periodicals; Environmentally induced diseases -- Periodicals; Toxicology -- Periodicals; 615.9005
• DOI: 10.1002/jat.2827
• Languages: English
• ISSNs: 0260-437X

Abstract

ABSTRACT: Osteoclasts (OCLs) are multinucleated bone‐resorbing cells that are differentiated by receptor activator of nuclear factor kappa‐B ligand (RANKL) and macrophage colony‐stimulating factor (M‐CSF). Our recent studies have shown that heme‐oxygenase‐1 (HO‐1), a stress‐induced cytoprotective enzyme, plays an important role in OCL differentiation, although the pharmacological significance of this effect remains unknown. In this study, we investigated the effects of tert ‐butylhydroquinone (tBHQ), a pharmacological HO‐1 inducer, on in vitro differentiation of bone marrow‐derived macrophages (BMMs) or murine monocytic cell line RAW‐D into OCLs. tBHQ inhibited the formation and the bone‐resorbing activity of OCLs. Moreover, tBHQ treatment decreased the expression of nuclear factor of activated T cells cytoplasmic‐1 (NFATc1), a master regulator of OCL differentiation, and of OCL markers transcriptionally regulated by NFATc1, such as Src and cathepsin K. In addition, tBHQ impaired phosphorylation of extracellular signal‐regulated kinase, p38 mitogen‐activated protein kinase (MAPK), Jun N‐terminal kinase, Akt, and inhibitor of nuclear factor kappa B alpha (IκBα). Finally, we show that tBHQ inhibited the release of high mobility group box 1 (HMGB1), a recently identified activator of OCL differentiation. Thus, tBHQ inhibits OCL differentiation through the HO‐1/HMGB1 pathways. Copyright © 2012 John Wiley & Sons, Ltd. Abstract : Osteoclasts (OCLs) are multinucleated bone‐resorbing cells. In this study, we investigated the effects of tert ‐butylhydroquinone (tBHQ) on differentiation of macrophages into OCLs. tBHQ treatment decreased the expression of nuclear factor of activated T cells cytoplasmic‐1 (NFATc1) and impaired phosphorylation of several mitogen‐activated protein kinases. And, tBHQ inhibited the release of high mobility group box 1 (HMGB1), a recently identified activator of OCL differentiation. Thus, tBHQ inhibits OCL differentiation through the HO‐1/HMGB1/NFATc1 pathways.