Inhibition of sphingosine 1-phosphate protects mice against chondrocyte catabolism and osteoarthritis.
Bone
Cartilage
Metalloproteinase
Osteoarthritis
Sphingosine 1 phosphate
Journal
Osteoarthritis and cartilage
ISSN: 1522-9653
Titre abrégé: Osteoarthritis Cartilage
Pays: England
ID NLM: 9305697
Informations de publication
Date de publication:
09 2021
09 2021
Historique:
received:
11
02
2021
revised:
18
05
2021
accepted:
07
06
2021
pubmed:
19
6
2021
medline:
23
2
2022
entrez:
18
6
2021
Statut:
ppublish
Résumé
Cartilage loss observed in osteoarthritis (OA) is prevented when osteoclasts in the subchondral bone are inhibited in mice. Here, we investigated the role of the osteoclast secretome and of the lipid mediator sphingosine 1-phosphate (S1P) in chondrocyte metabolism and OA. We used SphK1 The osteoclast secretome increased the expression of Mmp3 and Mmp13 in murine chondrocytes and cartilage explants and activated the JNK signaling pathway, which led to matrix degradation. JTE013 reversed the osteoclast-mediated chondrocyte catabolism and protected mice against OA, suggesting that osteoclastic S1P contributes to cartilage damage in OA via S1P/S1P Lack of S1P in myeloid cells and local S1P neutralization alleviates from osteoarthritis in mice. These data identify S1P as a therapeutic target in OA.
Identifiants
pubmed: 34144150
pii: S1063-4584(21)00807-4
doi: 10.1016/j.joca.2021.06.001
pii:
doi:
Substances chimiques
Lysophospholipids
0
sphingosine 1-phosphate
26993-30-6
Sphingosine
NGZ37HRE42
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1335-1345Informations de copyright
Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.