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Expression of cathepsin K and MMP-1 indicate persistent osteodestruktive activity in longstanding ankylosing spondylitis
  1. Michel Neidhart (michel.neidhart{at}usz.ch)
  1. WHO Collaboratory Center for Molecular Biology, University Hospital Zürich, Switzerland
    1. Xenofon Baraliakos (xenob{at}onlinehome.de)
    1. Rheumazentrum Ruhrgebiet, Ruhr-University Bochum, Germany
      1. Christian Seemayer (christian.a.seemayer{at}hcuge.ch)
      1. WHO Collaboratory Center for Molecular Biology, University Hospital Zürich, Switzerland
        1. Caren Zelder (dirksuhl{at}aol.com)
        1. WHO Collaboratory Center for Molecular Biology, University Hospital Zürich, Switzerland
          1. Renate E Gay (renate.gay{at}usz.ch)
          1. WHO Collaboratory Center for Molecular Biology, University Hospital Zürich, Switzerland
            1. Beat A Michel (beat.michel{at}usz.ch)
            1. University Zurich, Switzerland
              1. Heinrich Boehm (boehmbadberka{at}aol.com)
              1. Clinic for Orthopaedics Spinal Surgery and Paraplegiology, Bad Berka, Germany
                1. Steffen Gay (steffen.gay{at}usz.ch)
                1. WHO Collaboratory Center for Molecular Biology, University Hospital Zürich, Switzerland
                  1. Jürgen Braun (j.braun{at}rheumazentrum-ruhrgebiet.de)
                  1. Rheumazentrum Ruhrgebiet, Germany

                    Abstract

                    Background: Ankylosing spondylitis (AS) is a frequent largely genetically determined rheumatic disease that is characterised by spinal inflammation and new bone formation. However, the exact pathogenesis including pathology is still not clear.

                    Objective: To analyse tissue obtained at spinal surgery by immunohistochemistry and compare the specimen of patients with AS to those with degenerative disc disease (DDD).

                    Methods: Bony and soft tissue specimens of 30 AS and 20 DDD patients were obtained during spinal osteotomy from different anatomic regions including articular and spinous processes, interspinous ligaments and intervertebral disks. Immunohistolochemistry was performed with established markers for cathepsin-K, MMP-1, MMP-3 and RANK-ligand.

                    Results: Cathepsin-K and MMP-1-positive cells were only observed in AS specimen. Cathepsin-K-positive multinucleated cells were detected at articular processes adjacent to fibrous tissues. MMP-1 was expressed in smaller mononuclear cells attached to bone, Invasion of bone by MMP-1 cells was seen at entheseal sites. In the intervertebral disks, most mononuclear cells were cathepsin-K-positive. Isolated cells expressing these matrix degrading enzymes found in DDD never showed signs of invasion. No differences were found for MMP-3 between AS and DDD. Clear expression of RANK ligand was only detected in one AS patient.

                    Conclusion Cathepsin-K is strongly expressed in different regions of the spine in AS. Mainly mononuclar cells, fibroblast-like cells, and cells attached to bone and at sites of bone remodelling expressed cathepsin K suggestive of high osteoclastic activity. This supports the role of persistent inflammation in the pathogenesis of AS. How these changes relate to osteoproliferation remains to be determined.

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