Increased RANKL-mediated osteoclastogenesis by interleukin-1ß and endoplasmic reticulum stress.
Joint Bone Spine
; 81(6): 520-6, 2014 Dec.
Article
em En
| MEDLINE
| ID: mdl-24956991
ABSTRACT
OBJECTIVE:
The mechanism by which IL-1ß 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-1ß, 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-1ß 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-1ß 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 eIF2α. siRNA-mediated knockdown of ER stress signals inhibited the expression of NFATc1 and c-Fos, thus reducing IL-1ß and/or TG-induced formation of osteoclasts.CONCLUSIONS:
Osteoclastogenesis by IL-1ß and/or ER stress is mainly associated with upregulation of eIF2α, 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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Osteoclastos
/
Células da Medula Óssea
/
Interleucina-1beta
/
Ligante RANK
/
Estresse do Retículo Endoplasmático
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Joint Bone Spine
Assunto da revista:
REUMATOLOGIA
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Coréia do Sul