Inhibition of Klf10 Attenuates Oxidative Stress-Induced Senescence of Chondrocytes via Modulating Mitophagy

Molecules. 2023 Jan 17;28(3):924. doi: 10.3390/molecules28030924.

Abstract

Osteoarthritis (OA) is the most prevalent degenerative joint disease in the elderly. Accumulation of evidence has suggested that chondrocyte senescence plays a significant role in OA development. Here, we show that Krüppel-like factor 10 (Klf10), also named TGFβ inducible early gene-1 (TIEG1), is involved in the pathology of chondrocyte senescence. Knocking down the Klf10 in chondrocytes attenuated the tert-butyl hydroperoxide (TBHP)-induced senescence, inhibited generation of reactive oxygen species (ROS), and maintained mitochondrial homeostasis by activating mitophagy. These findings suggested that knocking down Klf10 inhibited senescence-related changes in chondrocytes and improved cartilage homeostasis, indicating that Klf10 may be a therapeutic target for protecting cartilage against OA.

Keywords: Klf10; autophagy; mitochondria; osteoarthritis; senescence.

MeSH terms

  • Aged
  • Cartilage, Articular* / metabolism
  • Cellular Senescence / physiology
  • Chondrocytes / pathology
  • Early Growth Response Transcription Factors / metabolism
  • Humans
  • Kruppel-Like Transcription Factors / genetics
  • Kruppel-Like Transcription Factors / metabolism
  • Mitophagy
  • Osteoarthritis* / drug therapy
  • Oxidative Stress / physiology
  • Reactive Oxygen Species / metabolism

Substances

  • Reactive Oxygen Species
  • KLF10 protein, human
  • Kruppel-Like Transcription Factors
  • Early Growth Response Transcription Factors