LTF ameliorates cartilage endplate degeneration by suppressing calcification, senescence and matrix degradation through the JAK2/STAT3 pathway

J Cell Mol Med. 2024 Oct;28(19):e18267. doi: 10.1111/jcmm.18267.

Abstract

Intervertebral disc degeneration (IDD)-induced cervical and lumbar herniations are debilitating diseases. The function of intervertebral disc (IVD) mainly depends on the cartilage endplate (CEP), which provides support and waste removal. Therefore, IDD stems from the degeneration of CEP. Our study shows that the expression of lactotransferrin (LTF), an iron-binding protein, is significantly decreased in degenerated human and rat CEP tissues. In addition, we found that LTF knockdown promoted calcification, senescence, and extracellular matrix (ECM) degradation in human endplate chondrocytes. Furthermore, the in vivo experiment results confirmed that the JAK2/STAT3 pathway inhibitor AG490 significantly reversed these effects. In addition to investigating the role and mechanism of LTF in CEP degeneration, this study provides a theoretical basis and experimental evidence to improve IDD treatment.

Keywords: JAK2/STAT3 pathway; calcification; cartilage endplate degeneration; extracellular matrix degradation; lactotransferrin; senescence.

MeSH terms

  • Adult
  • Animals
  • Calcinosis / genetics
  • Calcinosis / metabolism
  • Calcinosis / pathology
  • Cartilage / metabolism
  • Cartilage / pathology
  • Cellular Senescence
  • Chondrocytes* / metabolism
  • Chondrocytes* / pathology
  • Extracellular Matrix* / metabolism
  • Female
  • Humans
  • Intervertebral Disc Degeneration* / genetics
  • Intervertebral Disc Degeneration* / metabolism
  • Intervertebral Disc Degeneration* / pathology
  • Janus Kinase 2* / metabolism
  • Male
  • Middle Aged
  • Rats
  • Rats, Sprague-Dawley
  • STAT3 Transcription Factor* / metabolism
  • Signal Transduction*

Substances

  • STAT3 Transcription Factor
  • Janus Kinase 2