Inflammatory mediators in osteoarthritis

M. Beekhuizen

Research output: ThesisDoctoral thesis 1 (Research UU / Graduation UU)

Abstract

Osteoarthritis (OA) is a degenerative joint disorder involving cartilage destruction and joint inflammation. Despite extensive research, still much is unknown on the pathogenesis and aetiology of OA. Inflammation and inflammatory mediators (both local and systemic) are key in the pathogenesis of OA. For rheumatoid arthritis, multiple therapies are based on targeting the mediators that are associated with inflammation and joint destruction. Motivated by these findings we set off to identify which inflammatory mediators play a role in OA and whether interfering with these inflammatory mediators could stop OA progression or aid in cartilage repair and regeneration. In this thesis we identified multiple inflammatory mediators and clusters associated with joint inflammation. In a co-culture the mediators produced by OA synovial tissue and cartilage closely resembles the joint environment as measured in OA synovial fluid. Moreover, specific inflammatory mediators produced by the synovial tissue, such as OSM, are capable of slowing down cartilage repair. When the production of inflammatory mediators was decreased by anti-inflammatory drugs or by interference with specific mediators (i.e. OSM), chondrocyte metabolism was affected and cartilage repair improved. We showed that intervention with the production or activity of inflammatory mediators by synovial tissue plays an import role in cartilage metabolism and maybe could stop OA progression.
Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
  • University Medical Center (UMC) Utrecht
Supervisors/Advisors
  • Dhert, W.J.A., Primary supervisor, External person
  • van Osch, G.J.V.M., Supervisor, External person
  • Creemers, Laura, Co-supervisor
Award date3 Jul 2014
Publisher
Print ISBNs978-90-9028322-7
Publication statusPublished - 3 Jul 2014

Keywords

  • Osteoarthritis
  • inflammation
  • mediators
  • cartilage repair
  • identification

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