Inhibition of receptor activator of nuclear factor-κB ligand- or lipopolysaccharide-induced osteoclast formation by conophylline through downregulation of CREB
| Autor: | Takashi Yokochi, Jambalganiin Ulziisaikhan, Erdenezaya Odkhuu, Kazuo Umezawa, Naoki Koide, Tamami Ukaji, Yuichiro Kondo |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Lipopolysaccharides
musculoskeletal diseases MAPK/ERK pathway Immunology Down-Regulation Osteoclasts Bone Marrow Cells CREB Cell Line Osteoclast maturation Mice chemistry.chemical_compound Osteoclast medicine Animals Immunology and Allergy Calcitonin receptor Cyclic AMP Response Element-Binding Protein Vinca Alkaloids NFATC Transcription Factors biology Chemistry Activator (genetics) RANK Ligand NF-kappa B NF-κB Cell biology medicine.anatomical_structure Gene Expression Regulation RANKL Cancer research biology.protein Mitogen-Activated Protein Kinases Proto-Oncogene Proteins c-fos Signal Transduction |
| Zdroj: | Immunology Letters. 161:31-37 |
| ISSN: | 0165-2478 |
| DOI: | 10.1016/j.imlet.2014.04.006 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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