Osmolarity‐Induced Altered Intracellular Molecular Crowding Drives Osteoarthritis Pathology

Autor: Kannan Govindaraj, Marieke Meteling, Jeroen vanRooij, Malin Becker, Andre J. vanWijnen, Jeroen J. J. P. vanden Beucken, Yolande F. M. Ramos, Joyce vanMeurs, Janine N. Post, Jeroen Leijten
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Advanced Science, Vol 11, Iss 11, Pp n/a-n/a (2024)
Druh dokumentu: article
ISSN: 2198-3844
20230672
DOI: 10.1002/advs.202306722
Popis: 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.
Databáze: Directory of Open Access Journals
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