HSP90 Exacerbates Bone Destruction in Rheumatoid Arthritis by Activating TRAF6/NFATc1 Signaling.
Inflammation
; 47(1): 363-375, 2024 Feb.
Article
em En
| MEDLINE
| ID: mdl-37902841
Rheumatoid arthritis (RA) is an autoimmune disease characterized by a notably high disability rate, primarily attributed to cartilage and bone degradation. The involvement of heat shock protein 90 (HSP90) as a molecular chaperone in the inflammatory response of RA has been established, but its role in bone destruction remains uncertain. In the present study, the expression of HSP90 was augmented in osteoclasts induced by the receptor activator of nuclear factor-κB ligand. Additionaly, it was observed that the outcomes revealed a noteworthy inhibition of osteoclast formation and differentation when triptolide was utilized to hinder the expression of HSP90. Furthermore, the positive influence of HSP90 in osteoclast differentiation was substantiated by overexpressing HSP90 in osteoclast precursor cells. Mechanically, HSP90 significantly activated the TNF receptor-associated factor 6 (TRAF6)/Nuclear factor of activated T cells 1 (NFATc1) signaling axis, accompanied by markedly promoting osteoclast differentiation. This effect was consistently observed in the destructive joint of rats with collagen-induced arthritis, where HSP90 effectively activated osteoclasts and contributed to arthritic bone destruction by activating the TRAF6/NFATc1 signaling. Overall, the findings of this study provide compelling evidence that HSP90 exacerbates bone destruction in RA by promoting osteoclast differentiation through the activation of TRAF6/NFATc1 signaling, and interference with HSP90 may be a promising strategy for the discovery of anti-arthritic bone destruction agents.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Artrite Reumatoide
/
Reabsorção Óssea
Limite:
Animals
Idioma:
En
Revista:
Inflammation
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China
País de publicação:
Estados Unidos