FGF1 reduces cartilage injury in osteoarthritis via regulating AMPK/Nrf2 pathway

J Mol Histol. 2023 Oct;54(5):427-438. doi: 10.1007/s10735-023-10143-8. Epub 2023 Sep 2.

Abstract

Osteoarthritis (OA) is a systemic joint degenerative disease involving a variety of cytokines and growth factors. In this study, we investigated the protective effect of fibroblast growth factor 1 (FGF1) knockdown on OA and its underlying mechanisms in vitro. In addition, we evaluated the effect of FGF1 knockout on the destabilization of the medial meniscus (DMM) and examined the anterior and posterior cruciate ligament model in vivo. FGF1 affects OA cartilage destruction by increasing the protein expression of Nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1), which is associated with the phosphorylation of AMPK and its substrates. Our study showed that FGF1 knockdown could reverse the oxidative damage associated with osteoarthritis. Nrf2 knockdown eliminated the antioxidant effect of FGF1 knockdown on chondrocytes. Furthermore, AMPK knockdown could stop the impact of FGF1 knockdown on osteoarthritis. These findings suggested that FGF1 knockdown could effectively prevent and reverse osteoarthritis by activating AMPK and Nrf2 in articular chondrocytes.

Keywords: Amp-activated protein kinase; Fibroblast growth factor 1; Nuclear factor erythroid 2 related factor 2; Osteoarthritis.

MeSH terms

  • AMP-Activated Protein Kinases / metabolism
  • Cartilage / metabolism
  • Cartilage, Articular* / metabolism
  • Chondrocytes / metabolism
  • Fibroblast Growth Factor 1 / metabolism
  • Fibroblast Growth Factor 1 / pharmacology
  • Humans
  • NF-E2-Related Factor 2 / metabolism
  • Osteoarthritis* / metabolism

Substances

  • Fibroblast Growth Factor 1
  • NF-E2-Related Factor 2
  • AMP-Activated Protein Kinases