Osmolarity-Induced Altered Intracellular Molecular Crowding Drives Osteoarthritis Pathology

Kannan Govindaraj, Marieke Meteling, Jeroen van Rooij, Malin Becker, Andre J. van Wijnen, Jeroen J.J.P. van den Beucken, Yolande F.M. Ramos, Joyce van Meurs, Janine N. Post, Jeroen Leijten*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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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.

Original languageEnglish
Article number2306722
Number of pages14
JournalAdvanced science
Volume11
Issue number11
Early online date11 Jan 2024
DOIs
Publication statusPublished - 20 Mar 2024

Keywords

  • cell volume
  • intracellular molecular crowding
  • osteoarthritis
  • pathology

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