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Increased RANKL-mediated osteoclastogenesis by interleukin-1β and endoplasmic reticulum stress : Increased RANKL-mediated osteoclastogenesis by interleukin-1 beta and endoplasmic reticulum stress
Cited 21 time in
Web of Science
Cited 24 time in Scopus
- Authors
- Issue Date
- 2014-12
- Publisher
- Elsevier Masson
- Citation
- Joint Bone Spine, Vol.81 No.6, pp.520-526
- Abstract
- Objective: The mechanism by which IL-1 beta and thapsigargin (TG)-induced endoplasmic reticulum (ER) stress modulate the receptor activator of nuclear factor kappa-B ligand (RANKL)-mediated osteoclastogenesis remains elusive. Thus, we investigated the osteoclast-specific and ER signals in osteoclastogenesis of bone marrow-derived cells. Methods: Bone marrow cells (BMCs) were obtained from 5-week-old male ICR mice and cultured to be differentiated into osteoclasts with M-CSF and RANKL in the presence or absence of IL-1 beta, TG, or 4-phenylbutyric acid (PBA), an ER stress-reducing drug. The formation of osteoclasts was evaluated by tartrate-resistant acid phosphatase (TRAP) staining and resorption pit assay with a dentine slice. The molecular mechanism of IL-1 beta and ER stress in osteoclastogenesis was investigated in BMCs transfected with siRNA for GRP78, PERK and IRE1 using reverse transcription-polymerase chain reaction and immunoblotting for osteoclast-specific and ER stress signaling molecules. Results: IL-1 beta and ER stress induced by TG-augmented the formation of osteoclasts, which was significantly inhibited by PBA and was mediated with osteoclast-specific signals, including c-Fos, NFATc1, and ER stress-associated signaling pathways, such as PERK, IRE1, GRP78, and eIF2 alpha. siRNA-mediated knockdown of ER stress signals inhibited the expression of NFATc1 and c-Fos, thus reducing IL-1 beta and/or TG-induced formation of osteoclasts. Conclusions: Osteoclastogenesis by IL-1 beta and/or ER stress is mainly associated with upregulation of eIF2 alpha, GRP78, PERK and IRE1. These results suggest that the signaling pathway of ER stress-induced osteoclast formation might be a new therapeutic target to prevent inflammatory and destructive arthritic disease such as RA and diverse osteoporosis. (C) 2014 Societe francaise de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.
- ISSN
- 1297-319X
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