Osmolarity-Induced Altered Intracellular Molecular Crowding Drives Osteoarthritis Pathology.
Adv Sci (Weinh)
; 11(11): e2306722, 2024 Mar.
Article
en En
| MEDLINE
| ID: mdl-38213111
ABSTRACT
Osteoarthritis (OA) is a multifactorial degenerative joint disease of which the underlying mechanisms are yet to be fully understood. At the molecular level, multiple factors including altered signaling pathways, epigenetics, metabolic imbalance, extracellular matrix degradation, production of matrix metalloproteinases, and inflammatory cytokines, are known to play a detrimental role in OA. However, these factors do not initiate OA, but are mediators or consequences of the disease, while many other factors causing the etiology of OA are still unknown. Here, it is revealed that microenvironmental osmolarity can induce and reverse osteoarthritis-related behavior of chondrocytes via altered intracellular molecular crowding, which represents a previously unknown mechanism underlying OA pathophysiology. Decreased intracellular crowding is associated with increased sensitivity to proinflammatory triggers and decreased responsiveness to anabolic stimuli. OA-induced lowered intracellular molecular crowding could be renormalized via exposure to higher extracellular osmolarity such as those found in healthy joints, which reverse OA chondrocyte's sensitivity to catabolic stimuli as well as its glycolytic metabolism.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Osteoartritis
/
Cartílago Articular
Límite:
Humans
Idioma:
En
Revista:
Adv Sci (Weinh)
/
Advanced science (Weinheim)
Año:
2024
Tipo del documento:
Article
País de afiliación:
Países Bajos