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Inhibition of receptor activator of nuclear factor-κB ligand- or lipopolysaccharide-induced osteoclast formation by conophylline through downregulation of CREB.
Immunol Lett. 2014 Sep; 161(1):31-7.IL

Abstract

The effect of conophylline (CNP) on the receptor activator of nuclear factor-κB ligand (RANKL) or lipopolysaccharide (LPS)-induced osteoclast formation was studied in vitro using bone marrow-derived macrophages (BMMs) or the mouse macrophage-like cell line RAW 264.7. CNP inhibited RANKL-induced formation of osteoclasts identified as tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells in a culture of BMMs. It also inhibited RANKL- or LPS-induced osteoclast formation in RAW 264.7 cells. CNP lowered the osteoclast maturation markers such as calcitonin receptor, MMP9 and cathepsin K in BMMs, suggesting that CNP would inhibit the process of osteoclast differentiation. CNP inhibited the RANKL-induced expressions of c-Fos and nuclear factor of activated T cells (NFATc1), key transcription factors for osteoclastogenesis. On the other hand, CNP did not inhibit the signaling pathway of NF-κB and mitogen-activated protein kinases (MAPKs) in RANKL-stimulated BMMs. Interestingly, CNP inhibited RANKL-induced CREB activation that can mediate c-Fos and NFATc1. CNP also inhibited RANKL- or LPS-induced CREB, c-Fos and NFATc1 activation in RAW 264.7 cells. We have previously found that CNP directly binds to ADP-ribosylation-like factor-6 interacting protein (ARL6ip), although its role in osteoclastogenesis is not clear. Gene knockdown of ARL6ip by siRNA inhibited RANKL-induced c-Fos expression, suggesting that inactivation of ARL6ip may be involved in an inhibitory effect of CNP. Taken together, CNP was shown to inhibit osteoclast formation possibly via CREB inactivation following a decrease in c-Fos and NFATc1 expression.

Authors+Show Affiliations

Department of Microbiology and Immunology, Aichi Medical University School of Medicine, Nagakute, Japan. Electronic address: koide@aichi-med-u.ac.jp.Department of Applied Chemistry, Faculty of Science and Technology, Keio University, Yokohama, Japan.Department of Microbiology and Immunology, Aichi Medical University School of Medicine, Nagakute, Japan.Department of Microbiology and Immunology, Aichi Medical University School of Medicine, Nagakute, Japan.Department of Molecular Target Medicine Screening, Aichi Medical University School of Medicine, Nagakute, Japan.Department of Microbiology and Immunology, Aichi Medical University School of Medicine, Nagakute, Japan.Department of Molecular Target Medicine Screening, Aichi Medical University School of Medicine, Nagakute, Japan.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24792671

Citation

Koide, Naoki, et al. "Inhibition of Receptor Activator of Nuclear factor-κB Ligand- or Lipopolysaccharide-induced Osteoclast Formation By Conophylline Through Downregulation of CREB." Immunology Letters, vol. 161, no. 1, 2014, pp. 31-7.
Koide N, Kondo Y, Odkhuu E, et al. Inhibition of receptor activator of nuclear factor-κB ligand- or lipopolysaccharide-induced osteoclast formation by conophylline through downregulation of CREB. Immunol Lett. 2014;161(1):31-7.
Koide, N., Kondo, Y., Odkhuu, E., Ulziisaikhan, J., Ukaji, T., Yokochi, T., & Umezawa, K. (2014). Inhibition of receptor activator of nuclear factor-κB ligand- or lipopolysaccharide-induced osteoclast formation by conophylline through downregulation of CREB. Immunology Letters, 161(1), 31-7. https://doi.org/10.1016/j.imlet.2014.04.006
Koide N, et al. Inhibition of Receptor Activator of Nuclear factor-κB Ligand- or Lipopolysaccharide-induced Osteoclast Formation By Conophylline Through Downregulation of CREB. Immunol Lett. 2014;161(1):31-7. PubMed PMID: 24792671.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inhibition of receptor activator of nuclear factor-κB ligand- or lipopolysaccharide-induced osteoclast formation by conophylline through downregulation of CREB. AU - Koide,Naoki, AU - Kondo,Yuichiro, AU - Odkhuu,Erdenezaya, AU - Ulziisaikhan,Jambalganiin, AU - Ukaji,Tamami, AU - Yokochi,Takashi, AU - Umezawa,Kazuo, Y1 - 2014/05/02/ PY - 2013/11/06/received PY - 2014/03/18/revised PY - 2014/04/07/accepted PY - 2014/5/6/entrez PY - 2014/5/6/pubmed PY - 2015/3/31/medline KW - ARL6ip KW - CREB KW - Conophylline KW - Lipopolysaccharide KW - Osteoclast KW - Receptor activator of nuclear factor-κB ligand SP - 31 EP - 7 JF - Immunology letters JO - Immunol. Lett. VL - 161 IS - 1 N2 - The effect of conophylline (CNP) on the receptor activator of nuclear factor-κB ligand (RANKL) or lipopolysaccharide (LPS)-induced osteoclast formation was studied in vitro using bone marrow-derived macrophages (BMMs) or the mouse macrophage-like cell line RAW 264.7. CNP inhibited RANKL-induced formation of osteoclasts identified as tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells in a culture of BMMs. It also inhibited RANKL- or LPS-induced osteoclast formation in RAW 264.7 cells. CNP lowered the osteoclast maturation markers such as calcitonin receptor, MMP9 and cathepsin K in BMMs, suggesting that CNP would inhibit the process of osteoclast differentiation. CNP inhibited the RANKL-induced expressions of c-Fos and nuclear factor of activated T cells (NFATc1), key transcription factors for osteoclastogenesis. On the other hand, CNP did not inhibit the signaling pathway of NF-κB and mitogen-activated protein kinases (MAPKs) in RANKL-stimulated BMMs. Interestingly, CNP inhibited RANKL-induced CREB activation that can mediate c-Fos and NFATc1. CNP also inhibited RANKL- or LPS-induced CREB, c-Fos and NFATc1 activation in RAW 264.7 cells. We have previously found that CNP directly binds to ADP-ribosylation-like factor-6 interacting protein (ARL6ip), although its role in osteoclastogenesis is not clear. Gene knockdown of ARL6ip by siRNA inhibited RANKL-induced c-Fos expression, suggesting that inactivation of ARL6ip may be involved in an inhibitory effect of CNP. Taken together, CNP was shown to inhibit osteoclast formation possibly via CREB inactivation following a decrease in c-Fos and NFATc1 expression. SN - 1879-0542 UR - https://www.unboundmedicine.com/medline/citation/24792671/Inhibition_of_receptor_activator_of_nuclear_factor_κB_ligand__or_lipopolysaccharide_induced_osteoclast_formation_by_conophylline_through_downregulation_of_CREB_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0165-2478(14)00075-3 DB - PRIME DP - Unbound Medicine ER -