Kaempferol attenuates the effects of XIST/miR-130a/STAT3 on inflammation and extracellular matrix degradation in osteoarthritis

Future Med Chem. 2021 Sep;13(17):1451-1464. doi: 10.4155/fmc-2021-0127. Epub 2021 Jun 14.

Abstract

Aim: To investigate whether kaempferol exhibited protective effects on osteoarthritis chondrocytes by modulating the XIST/miR-130a/STAT3 axis. Methods: qRT-PCR and western blot assays were used for gene and protein determination. Dual luciferase reporter and RNA immunoprecipitation assays were employed to study the interaction between miRNA and lncRNA or genes. Results: Kaempferol decreased proinflammatory cytokine production and extracellular matrix degradation in C28/I2 cells. Additionally, kaempferol ameliorated XIST expression and enhanced miR-130a expression. XIST interacted with miR-130a, and STAT3 was identified as a target of miR-130a. Knockdown of XIST expression suppressed proinflammatory cytokine production and extracellular matrix degradation in C28/I2 cells. Overexpression of STAT3 rescued the effects of XIST knockdown. Conclusion: Kaempferol inhibited inflammation and extracellular matrix degradation by modulating the XIST/miR-130a/STAT3 axis in chondrocytes.

Keywords: STAT3; XIST; extracellular matrix degradation; kaempferol; miR-130a; osteoarthritis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Cytokines / antagonists & inhibitors
  • Cytokines / biosynthesis
  • Dose-Response Relationship, Drug
  • Extracellular Matrix / drug effects*
  • Extracellular Matrix / metabolism
  • Humans
  • Inflammation / drug therapy*
  • Inflammation / metabolism
  • Kaempferols / pharmacology*
  • MicroRNAs / genetics*
  • Osteoarthritis / drug therapy*
  • Osteoarthritis / metabolism
  • RNA, Long Noncoding / antagonists & inhibitors
  • RNA, Long Noncoding / genetics
  • STAT3 Transcription Factor / antagonists & inhibitors
  • STAT3 Transcription Factor / genetics

Substances

  • Cytokines
  • Kaempferols
  • MIRN130 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • XIST non-coding RNA
  • kaempferol