Effects of visfatin on intracellular mechanics and catabolism in human primary chondrocytes through glycogen synthase kinase 3β inactivation

Shun Fu Chang, Kuo Chin Huang, Kuan Han Lee, Yao Chang Chiang, Wei Ru Lee, Rong Ze Hsieh, Yu Ping Su*, Shun Chi Wu*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

5 Scopus citations

Abstract

Osteoarthritis (OA) is still a recalcitrant musculoskeletal disease on account of its complex biochemistry and mechanical stimulations. Apart from stimulation by external mechanical forces, the regulation of intracellular mechanics in chondrocytes has also been linked to OA development. Recently, visfatin has received significant attention because of the clinical finding of the positive correlation between its serum/synovial level and OA progression. However, the precise mechanism involved is still unclear. This study determined the effect of visfatin on intracellular mechanics and catabolism in human primary chondrocytes isolated from patients. The intracellular stiffness of chondrocytes was analyzed by the particle‐tracking microrheology method. It was shown that visfatin damages the microtubule and microfilament networks to influence intracellular mechanics to decrease the intracellular elasticity and viscosity via glycogen synthase kinase 3β (GSK3β) inac-tivation induced by p38 signaling. Further, microtubule network destruction in human primary chondrocytes is predominantly responsible for the catabolic effect of visfatin on the cyclooxygenase 2 upregulation. The present study shows a more comprehensive interpretation of OA development induced by visfatin through biochemical and biophysical perspectives. Finally, the role of GSK3β inactivation, and subsequent regulation of intracellular mechanics, might be considered as theranostic targets for future drug development for OA.

Original languageEnglish
Article number8107
JournalInternational Journal of Molecular Sciences
Volume22
Issue number15
DOIs
StatePublished - 01 08 2021

Bibliographical note

Publisher Copyright:
© 2021 by the authors. Li-censee MDPI, Basel, Switzerland.

Keywords

  • Elasticity
  • Glycogen synthase kinase 3β
  • Intracellular mechanics
  • Osteoarthritis
  • Primary human chondrocytes
  • Viscosity
  • Visfatin

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