The protective role of the 3-mercaptopyruvate sulfurtransferase (3-MST)-hydrogen sulfide (H<sub>2</sub>S) pathway against experimental osteoarthritis.
Détails
Etat: Public
Version: Final published version
Licence: CC BY 4.0
ID Serval
serval:BIB_BA8A3C5DF659
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
The protective role of the 3-mercaptopyruvate sulfurtransferase (3-MST)-hydrogen sulfide (H<sub>2</sub>S) pathway against experimental osteoarthritis.
Périodique
Arthritis research & therapy
ISSN
1478-6362 (Electronic)
ISSN-L
1478-6354
Statut éditorial
Publié
Date de publication
17/03/2020
Peer-reviewed
Oui
Volume
22
Numéro
1
Pages
49
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: epublish
Publication Status: epublish
Résumé
Osteoarthritis (OA) is characterized by the formation and deposition of calcium-containing crystals in joint tissues, but the underlying mechanisms are poorly understood. The gasotransmitter hydrogen sulfide (H <sub>2</sub> S) has been implicated in mineralization but has never been studied in OA. Here, we investigated the role of the H <sub>2</sub> S-producing enzyme 3-mercaptopyruvate sulfurtransferase (3-MST) in cartilage calcification and OA development.
3-MST expression was analyzed in cartilage from patients with different OA degrees, and in cartilage stimulated with hydroxyapatite (HA) crystals. The modulation of 3-MST expression in vivo was studied in the meniscectomy (MNX) model of murine OA, by comparing sham-operated to MNX knee cartilage. The role of 3-MST was investigated by quantifying joint calcification and cartilage degradation in WT and 3-MST <sup>-/-</sup> meniscectomized knees. Chondrocyte mineralization in vitro was measured in WT and 3-MST <sup>-/-</sup> cells. Finally, the effect of oxidative stress on 3-MST expression and chondrocyte mineralization was investigated.
3-MST expression in human cartilage negatively correlated with calcification and OA severity, and diminished upon HA stimulation. In accordance, cartilage from menisectomized OA knees revealed decreased 3-MST if compared to sham-operated healthy knees. Moreover, 3-MST <sup>-/-</sup> mice showed exacerbated joint calcification and OA severity if compared to WT mice. In vitro, genetic or pharmacologic inhibition of 3-MST in chondrocytes resulted in enhanced mineralization and IL-6 secretion. Finally, oxidative stress decreased 3-MST expression and increased chondrocyte mineralization, maybe via induction of pro-mineralizing genes.
3-MST-generated H <sub>2</sub> S protects against joint calcification and experimental OA. Enhancing H <sub>2</sub> S production in chondrocytes may represent a potential disease modifier to treat OA.
3-MST expression was analyzed in cartilage from patients with different OA degrees, and in cartilage stimulated with hydroxyapatite (HA) crystals. The modulation of 3-MST expression in vivo was studied in the meniscectomy (MNX) model of murine OA, by comparing sham-operated to MNX knee cartilage. The role of 3-MST was investigated by quantifying joint calcification and cartilage degradation in WT and 3-MST <sup>-/-</sup> meniscectomized knees. Chondrocyte mineralization in vitro was measured in WT and 3-MST <sup>-/-</sup> cells. Finally, the effect of oxidative stress on 3-MST expression and chondrocyte mineralization was investigated.
3-MST expression in human cartilage negatively correlated with calcification and OA severity, and diminished upon HA stimulation. In accordance, cartilage from menisectomized OA knees revealed decreased 3-MST if compared to sham-operated healthy knees. Moreover, 3-MST <sup>-/-</sup> mice showed exacerbated joint calcification and OA severity if compared to WT mice. In vitro, genetic or pharmacologic inhibition of 3-MST in chondrocytes resulted in enhanced mineralization and IL-6 secretion. Finally, oxidative stress decreased 3-MST expression and increased chondrocyte mineralization, maybe via induction of pro-mineralizing genes.
3-MST-generated H <sub>2</sub> S protects against joint calcification and experimental OA. Enhancing H <sub>2</sub> S production in chondrocytes may represent a potential disease modifier to treat OA.
Mots-clé
Animal model, Calcium-containing crystals, Chondrocyte calcification, Hydrogen sulfide, Osteoarthritis
Pubmed
Open Access
Oui
Création de la notice
01/04/2020 21:46
Dernière modification de la notice
30/04/2021 7:14