PMID- 31275508
OWN - NLM
STAT- MEDLINE
DCOM- 20200207
LR  - 20200225
IS  - 1942-0994 (Electronic)
IS  - 1942-0900 (Print)
IS  - 1942-0994 (Linking)
VI  - 2019
DP  - 2019
TI  - Auranofin Inhibits RANKL-Induced Osteoclastogenesis by Suppressing Inhibitors of 
      kappaB Kinase and Inflammasome-Mediated Interleukin-1beta Secretion.
PG  - 3503912
LID - 10.1155/2019/3503912 [doi]
LID - 3503912
AB  - Osteoporosis is a degenerative metabolic disease caused by an imbalance between 
      osteogenesis and osteoclastogenesis. Increased levels of proinflammatory 
      cytokines combined with decreased estrogen levels, which are commonly seen in 
      postmenopausal women, can lead to overactivation of osteoclasts. Therefore, 
      targeting osteoclast maturation may represent a novel strategy for both treating 
      and preventing osteoporosis. Auranofin is a gold-based compound first approved in 
      1985 for the treatment of rheumatic diseases. Here, we examined whether auranofin 
      suppresses osteoclast differentiation in vitro and in vivo. Auranofin was shown 
      to suppress receptor activator of NF-kappaB ligand- (RANKL-) induced 
      osteoclastogenesis in mouse bone marrow macrophages (BMMs) and Raw264.7 
      macrophages. Cotreatment of macrophages with auranofin blocked the RANKL-induced 
      inhibitors of kappaB kinase (IKK) phosphorylation, resulting in inhibition of nuclear 
      translocation of p65. The pan-caspase inhibitor nivocasan potently reduced not 
      only inflammasome-mediated interleukin-1beta (IL-1beta) secretion but also osteoclast 
      differentiation in BMMs. Auranofin suppressed inflammasome activation, as 
      evidenced by decreased production of cleaved IL-1beta in both bone marrow-derived 
      macrophages (BMDMs) and J774.A1 cells. Loss of both bone mass in ovariectomized 
      mice was significantly recovered by oral administration of auranofin. Taken 
      together, these data strongly support the use of auranofin for the prevention of 
      osteoclast-related osteoporosis.
FAU - Kim, Hyun Young
AU  - Kim HY
AD  - College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul 
      National University, Seoul 08826, Republic of Korea.
FAU - Kim, Kyeong Seok
AU  - Kim KS
AD  - College of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea.
FAU - Kim, Myung Ji
AU  - Kim MJ
AD  - College of Pharmacy, Chonnam National University, Gwangju 61186, Republic of 
      Korea.
FAU - Kim, Hyung-Shik
AU  - Kim HS
AD  - College of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea.
FAU - Lee, Kwang-Youl
AU  - Lee KY
AD  - College of Pharmacy, Chonnam National University, Gwangju 61186, Republic of 
      Korea.
FAU - Kang, Keon Wook
AU  - Kang KW
AUID- ORCID: 0000-0003-2867-8940
AD  - College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul 
      National University, Seoul 08826, Republic of Korea.
LA  - eng
PT  - Journal Article
DEP - 20190422
PL  - United States
TA  - Oxid Med Cell Longev
JT  - Oxidative medicine and cellular longevity
JID - 101479826
RN  - 0 (Antirheumatic Agents)
RN  - 0 (Inflammasomes)
RN  - 0 (NF-kappa B)
RN  - 3H04W2810V (Auranofin)
SB  - IM
MH  - Animals
MH  - Antirheumatic Agents/pharmacology/*therapeutic use
MH  - Auranofin/pharmacology/*therapeutic use
MH  - Female
MH  - Humans
MH  - Inflammasomes/*metabolism
MH  - Mice
MH  - NF-kappa B/*metabolism
MH  - Osteoclasts/cytology/*metabolism
MH  - Osteoporosis/*drug therapy/genetics/pathology
MH  - Transfection
PMC - PMC6561666
EDAT- 2019/07/06 06:00
MHDA- 2020/02/08 06:00
PMCR- 2019/04/22
CRDT- 2019/07/06 06:00
PHST- 2018/09/06 00:00 [received]
PHST- 2019/01/18 00:00 [revised]
PHST- 2019/01/28 00:00 [accepted]
PHST- 2019/07/06 06:00 [entrez]
PHST- 2019/07/06 06:00 [pubmed]
PHST- 2020/02/08 06:00 [medline]
PHST- 2019/04/22 00:00 [pmc-release]
AID - 10.1155/2019/3503912 [doi]
PST - epublish
SO  - Oxid Med Cell Longev. 2019 Apr 22;2019:3503912. doi: 10.1155/2019/3503912. 
      eCollection 2019.