eNAMPT is localised to areas of cartilage damage in patients with hip osteoarthritis and promotes cartilage catabolism and inflammation

Research output: Contribution to journalArticlepeer-review

Authors

  • Ashleigh M. Philp
  • Sam Butterworth
  • Edward T Davis
  • Simon Jones

Colleges, School and Institutes

External organisations

  • The Royal Orthopaedic Hospital NHS Foundation Trust
  • University of Birmingham
  • University of Manchester

Abstract

Obesity increases the risk of hip osteoarthritis (OA). Recent studies have shown that adipokine extracellular nicotinamide phosphoribosyltransferase (eNAMPT or visfatin) induces the production of IL-6 and matrix metalloproteases (MMPs) in chondrocytes, suggesting it may promote articular cartilage degradation. However, neither the functional effects of extracellular visfatin on human articular cartilage tissue, nor its expression in the joint of hip OA patients of varying BMI, have been reported. Hip OA joint tissues were collected from patients undergoing joint replacement surgery. Cartilage explants were stimulated with recombinant human visfatin. Pro-inflammatory cytokines and MMPs were measured by ELISA and Luminex. Localisation of visfatin expression in cartilage tissue was determined by immunohistochemistry. Cartilage matrix degradation was determined by quantifying proteoglycan release. Expression of visfatin was elevated in the synovial tissue of hip OA patients who were obese, and was co-localised with MMP-13 in areas of cartilage damage. Visfatin promoted the degradation of hip OA cartilage proteoglycan and induced the production of pro-inflammatory cytokines (IL-6, MCP-1, CCL20, and CCL4) and MMPs. The elevated expression of visfatin in the obese hip OA joint, and its functional effects on hip cartilage tissue, suggests it plays a central role in the loss of cartilage integrity in obese patients with hip OA.

Details

Original languageEnglish
Article number6719
JournalInternational Journal of Molecular Sciences
Volume22
Issue number13
Publication statusPublished - 23 Jun 2021

Sustainable Development Goals