Mechanical loading induces HIF-1α expression in chondrocytes via YAP

Biotechnol Lett. 2020 Sep;42(9):1645-1654. doi: 10.1007/s10529-020-02910-4. Epub 2020 May 25.

Abstract

Objectives: To investigate the role of YAP in cyclic mechanical stress induced up-regulation of HIF-1α in rat cartilage chondrocytes.

Results: Our in vitro and in vivo experiments demonstrated that cyclic mechanical stress promoted HIF-1α and YAP proteins expression in a magnitude dependent manner. Cyclic mechanical stress at 4000μ strain exhibited most significant effect in promoting HIF-1α and YAP up-regulation. Activation of YAP using LPA significantly promoted HIF-1α stabilization and expression, while YAP siRNA treatment suppressed the up-regulation of HIF-1α induced by cyclic mechanical stress.

Conclusion: Our results indicated that cyclic mechanical stress promoted HIF-1α stabilization and YAP is involved in mechanical stress induced HIF-1α up-regulation.

Keywords: Chondrocytes; Cyclic mechanical stress; HIF-1α; YAP.

MeSH terms

  • Animals
  • Apoptosis Regulatory Proteins* / genetics
  • Apoptosis Regulatory Proteins* / metabolism
  • Biomechanical Phenomena / physiology*
  • Cartilage, Articular / cytology
  • Cartilage, Articular / metabolism
  • Cells, Cultured
  • Chondrocytes* / metabolism
  • Chondrocytes* / physiology
  • Hypoxia-Inducible Factor 1, alpha Subunit* / genetics
  • Hypoxia-Inducible Factor 1, alpha Subunit* / metabolism
  • Male
  • Rats, Sprague-Dawley
  • Stress, Mechanical
  • Up-Regulation / genetics
  • YAP-Signaling Proteins

Substances

  • Apoptosis Regulatory Proteins
  • Hif1a protein, rat
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • YAP-Signaling Proteins
  • Yap1 protein, rat