PMID- 35231470
OWN - NLM
STAT- MEDLINE
DCOM- 20220407
LR  - 20220407
IS  - 1879-0712 (Electronic)
IS  - 0014-2999 (Linking)
VI  - 921
DP  - 2022 Apr 15
TI  - Urolithin A attenuates RANKL-induced osteoclastogenesis by co-regulating the p38 
      MAPK and Nrf2 signaling pathway.
PG  - 174865
LID - S0014-2999(22)00126-1 [pii]
LID - 10.1016/j.ejphar.2022.174865 [doi]
AB  - As a critical regulator of bone resorption. osteoclastogenesis is closely 
      associated with osteoporosis (OP) and commonly induced by receptor activator of 
      nuclear factor-kappaB ligand (RANKL), suggesting that suppression of inflammation may 
      improve OP. Urolithin A (UroA), an active metabolite of ellagic acid, is known to 
      exert anti-inflammatory and antioxidative effects. However, whether UroA 
      attenuates osteoclastogenesis remains unclear. Using a lipopolysaccharide 
      (LPS)-induced bone loss model, we evaluated the effects of UroA on inflammatory 
      osteoclastogenesis in mice and explored the potential mechanism from 
      RANKL-related signaling pathway. UroA significantly improved LPS-induced bone 
      loss and rescued the imbalance in bone microarchitecture parameters. 
      Hematoxylin&eosin (H&E) and tartrate resistant acid phosphatase (TRAP) staining 
      of femurs showed that UroA suppressed LPS-induced osteoclastogenesis accompanied 
      by the activation of nuclear factor-erythroid 2-related factor 2 (Nrf2) 
      signaling. In RANKL-triggered mouse bone marrow-derived macrophages (BMDMs), UroA 
      inhibited the formation of osteoclasts and Fibrous actin rings (F-actin rings), 
      and decreased TRAP activity. Moreover, UroA significantly decreased mRNA and 
      protein expression of major inflammatory cytokines in LPS-challenged 
      RAW264.7 cells by decreasing the phosphorylation of NF-kappaB p65, c-Jun N-terminal 
      kinase (JNK), extracellular signal regulated kinase1/2 (Erk1/2), and p38. 
      Furthermore, UroA may activate the Nrf2 signaling pathway by increasing mRNA and 
      protein expression of antioxidant proteins. We conclude that UroA attenuated 
      RANKL-induced osteoclastogenesis by suppressing the p38 mitogen-activated protein 
      kinase (MAPK) pathway and inducing Nrf2 nuclear translocation. Thus, 
      supplementation with UroA may help alleviate inflammation-induced bone loss and 
      bone resorption.
CI  - Copyright (c) 2022 Elsevier B.V. All rights reserved.
FAU - Wei, Wei
AU  - Wei W
AD  - The First Clinical Medical College, Nanjing University of Chinese Medicine, 
      Nanjing, 210023, China.
FAU - Peng, Chenjian
AU  - Peng C
AD  - Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese 
      Medicine, Nanjing, 210001, China.
FAU - Gu, Renjun
AU  - Gu R
AD  - The First Clinical Medical College, Nanjing University of Chinese Medicine, 
      Nanjing, 210023, China.
FAU - Yan, Xiwu
AU  - Yan X
AD  - The First Clinical Medical College, Nanjing University of Chinese Medicine, 
      Nanjing, 210023, China.
FAU - Ye, Jiapeng
AU  - Ye J
AD  - The First Clinical Medical College, Nanjing University of Chinese Medicine, 
      Nanjing, 210023, China.
FAU - Xu, Zhuicheng
AU  - Xu Z
AD  - School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, 
      China.
FAU - Sheng, Xianjie
AU  - Sheng X
AD  - School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, 
      China.
FAU - Huang, Guicheng
AU  - Huang G
AD  - The First Clinical Medical College, Nanjing University of Chinese Medicine, 
      Nanjing, 210023, China. Electronic address: hgc@njucm.edu.cn.
FAU - Guo, Yang
AU  - Guo Y
AD  - The First Clinical Medical College, Nanjing University of Chinese Medicine, 
      Nanjing, 210023, China. Electronic address: drguoyang@njucm.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20220226
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 (Coumarins)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (NF-kappa B)
RN  - 0 (RANK Ligand)
RN  - 1143-70-0 (3,8-dihydroxy-6H-dibenzo(b,d)pyran-6-one)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Animals
MH  - *Bone Resorption/drug therapy/metabolism
MH  - Cell Differentiation
MH  - Coumarins
MH  - Mice
MH  - NF-E2-Related Factor 2/metabolism
MH  - NF-kappa B/metabolism
MH  - Osteoclasts
MH  - Osteogenesis
MH  - *RANK Ligand/metabolism/pharmacology
MH  - Signal Transduction
MH  - p38 Mitogen-Activated Protein Kinases/metabolism
OTO - NOTNLM
OT  - MAPK
OT  - Nrf2
OT  - Osteoclastogenesis
OT  - Oxidative stress
OT  - Urolithin A
EDAT- 2022/03/02 06:00
MHDA- 2022/04/08 06:00
CRDT- 2022/03/01 20:13
PHST- 2021/08/06 00:00 [received]
PHST- 2022/01/17 00:00 [revised]
PHST- 2022/02/23 00:00 [accepted]
PHST- 2022/03/02 06:00 [pubmed]
PHST- 2022/04/08 06:00 [medline]
PHST- 2022/03/01 20:13 [entrez]
AID - S0014-2999(22)00126-1 [pii]
AID - 10.1016/j.ejphar.2022.174865 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 2022 Apr 15;921:174865. doi: 10.1016/j.ejphar.2022.174865. Epub 
      2022 Feb 26.