PMID- 24956991
OWN - NLM
STAT- MEDLINE
DCOM- 20150723
LR  - 20211203
IS  - 1778-7254 (Electronic)
IS  - 1297-319X (Linking)
VI  - 81
IP  - 6
DP  - 2014 Dec
TI  - Increased RANKL-mediated osteoclastogenesis by interleukin-1beta and endoplasmic 
      reticulum stress.
PG  - 520-6
LID - S1297-319X(14)00132-8 [pii]
LID - 10.1016/j.jbspin.2014.04.012 [doi]
AB  - OBJECTIVE: The mechanism by which IL-1beta 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-1beta, 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-1beta 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-1beta 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 eIF2alpha. siRNA-mediated 
      knockdown of ER stress signals inhibited the expression of NFATc1 and c-Fos, thus 
      reducing IL-1beta and/or TG-induced formation of osteoclasts. CONCLUSIONS: 
      Osteoclastogenesis by IL-1beta and/or ER stress is mainly associated with 
      upregulation of eIF2alpha, 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.
CI  - Copyright (c) 2014 Societe francaise de rhumatologie. Published by Elsevier SAS. 
      All rights reserved.
FAU - Lee, Eun-Gyeong
AU  - Lee EG
AD  - Department of Internal Medicine, Medical School and Research Institute of 
      Clinical Medicine, Chonbuk National University and Chonbuk, National University 
      Hospital, Jeonju, Jeonbuk 561-712, South Korea.
FAU - Sung, Myung-Soon
AU  - Sung MS
AD  - Department of Internal Medicine, Medical School and Research Institute of 
      Clinical Medicine, Chonbuk National University and Chonbuk, National University 
      Hospital, Jeonju, Jeonbuk 561-712, South Korea.
FAU - Yoo, Han-Gyul
AU  - Yoo HG
AD  - Department of Pharmacy Practice, College of Pharmacy, University of Rhode Island, 
      Kingston RI 02881, United States of America.
FAU - Chae, Han-Jung
AU  - Chae HJ
AD  - Department of Pharmacology, Chonbuk National University Medical School, Jeonju, 
      Jeonbuk 561-712, South Korea.
FAU - Kim, Hang-Rae
AU  - Kim HR
AD  - Department of Anatomy, Seoul National University College of Medicine, 103 
      Daehak-ro, Jongno-gu, Seoul 110-799, South Korea.
FAU - Yoo, Wan-Hee
AU  - Yoo WH
AD  - Department of Internal Medicine, Medical School and Research Institute of 
      Clinical Medicine, Chonbuk National University and Chonbuk, National University 
      Hospital, Jeonju, Jeonbuk 561-712, South Korea. Electronic address: 
      ywhim@jbnu.ac.kr.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140620
PL  - France
TA  - Joint Bone Spine
JT  - Joint bone spine
JID - 100938016
RN  - 0 (Endoplasmic Reticulum Chaperone BiP)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Hspa5 protein, mouse)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Phenylbutyrates)
RN  - 0 (RANK Ligand)
RN  - 67526-95-8 (Thapsigargin)
RN  - 7WY7YBI87E (4-phenylbutyric acid)
SB  - IM
MH  - Animals
MH  - Bone Marrow Cells/*metabolism
MH  - Cell Differentiation
MH  - Endoplasmic Reticulum Chaperone BiP
MH  - Endoplasmic Reticulum Stress/*physiology
MH  - Enzyme Inhibitors/pharmacology
MH  - Interleukin-1beta/*metabolism
MH  - Macrophages/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred ICR
MH  - Models, Animal
MH  - Osteoclasts/drug effects/*physiology
MH  - Phenylbutyrates
MH  - RANK Ligand/*metabolism
MH  - Signal Transduction
MH  - Thapsigargin/pharmacology
OTO - NOTNLM
OT  - 4-phenylbutyric acid
OT  - Endoplasmic reticulum stress
OT  - IL-1beta
OT  - Osteoclast
OT  - Thapsigargin
EDAT- 2014/06/25 06:00
MHDA- 2015/07/24 06:00
CRDT- 2014/06/25 06:00
PHST- 2013/08/25 00:00 [received]
PHST- 2014/04/24 00:00 [accepted]
PHST- 2014/06/25 06:00 [entrez]
PHST- 2014/06/25 06:00 [pubmed]
PHST- 2015/07/24 06:00 [medline]
AID - S1297-319X(14)00132-8 [pii]
AID - 10.1016/j.jbspin.2014.04.012 [doi]
PST - ppublish
SO  - Joint Bone Spine. 2014 Dec;81(6):520-6. doi: 10.1016/j.jbspin.2014.04.012. Epub 
      2014 Jun 20.