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Virchows Archiv

, Volume 449, Issue 1, pp 69–77 | Cite as

Stimulation of osteoclast formation by inflammatory synovial fluid

  • Iannis E. Adamopoulos
  • Lynett Danks
  • Ichiro Itonaga
  • Rachel M. Locklin
  • Afsie Sabokbar
  • David J. P. Ferguson
  • Nicholas A. AthanasouEmail author
Original Article

Abstract

Peri-articular bone resorption is a feature of arthritis due to crystal deposition and rheumatoid disease. Under these conditions, the synovial fluid contains numerous inflammatory cells that produce cytokines and growth factors which promote osteoclast formation. The aim of this study was to determine whether inflammatory synovial fluid stimulates the formation of osteoclasts. Synovial fluid from rheumatoid arthritis (RA), pyrophosphate arthropathy (PPA) and osteoarthritis (OA) patients was added to cultures (n=8) of human peripheral blood mononuclear cells (PBMCs) in the presence and absence of macrophage colony-stimulating factor (M-CSF) and the receptor activator of NF-κB ligand (RANKL). Osteoclast formation was assessed by the formation of cells positive for tartrate-resistant acid phosphatase (TRAP) and vitronectin receptor (VNR) and the extent of lacunar resorption. The addition of 10% OA, RA and PPA synovial fluid to PBMC cultures resulted in the formation of numerous multinucleated or mononuclear TRAP+ and VNR+ cells which were capable of lacunar resorption. In contrast to PBMC cultures incubated with OA synovial fluid, there was marked stimulation of osteoclast formation and resorption in cultures containing inflammatory RA and PPA synovial fluid which contained high levels of tumour necrosis factor alpha, a factor which is known to stimulate RANKL-induced osteoclast formation.

Keywords

Synovial fluid Rheumatoid arthritis Crystal Pyrophosphate Osteoclast 

Notes

Acknowledgements

This study was approved by the Oxford Research Ethics Committee. The authors wish to thank all the volunteers who kindly donated blood samples for this study. We also extend our thanks to Dr. David Lacey, Amgen Inc., for providing the soluble RANKL. This work was funded by Action Research and the Frances and Augustus Newman Foundation. I.A. is the recipient of a Research into Ageing DPhil studentship.

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Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Iannis E. Adamopoulos
    • 1
    • 4
  • Lynett Danks
    • 1
  • Ichiro Itonaga
    • 2
  • Rachel M. Locklin
    • 1
  • Afsie Sabokbar
    • 1
  • David J. P. Ferguson
    • 3
  • Nicholas A. Athanasou
    • 4
    Email author
  1. 1.Institute of Musculoskeletal Sciences, Botnar Research CentreUniversity of OxfordOxfordUK
  2. 2.Department of Orthopaedic SurgeryOita Medical UniversityOita-gunJapan
  3. 3.Nuffield Department of Clinical Laboratory ScienceJohn Radcliffe HospitalOxfordUK
  4. 4.Department of PathologyNuffield Orthopaedic CentreHeadingtonUK

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