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CTLA-4 directly inhibits osteoclast formation
  1. Roland Axmann
  1. Department of Internal Medicine 3, University of Erlangen, Germany
    1. Sonja Herman
    1. Department of Internal Medicine 3, University of Erlangen, Germany
      1. Mario Zaiss
      1. Department of Internal Medicine 3, University of Erlangen, Germany
        1. Sandra Franz
        1. Department of Internal Medicine 3, University of Erlangen, Germany
          1. Karin Polzer
          1. Department of Internal Medicine 3, University of Erlangen, Germany
            1. Jochen Zwerina
            1. Department of Internal Medicine 3, University of Erlangen, Germany
              1. Martin Herrmann
              1. Department of Internal Medicine 3, University of Erlangen, Germany
                1. Josef Smolen
                1. Department of Internal Medicine III, Medical University of Vienna, Austria
                  1. Georg Schett (georg.schett{at}uk-erlangen.de)
                  1. Department of Internal Medicine 3, University of Erlangen, Germany

                    Abstract

                    CTLA-4 is a regulator of co-stimulation and inhibits the activation of T cells through interfering with the interaction of CD80/86 on antigen presenting cells with CD28 on T cells. CTLA-4 binds to the surface of antigen presenting cells, such as dendritic cells and monocytes through CD80/86. Monocytes can differentiate in osteoclasts, the primary bone resorbing cells. Herein, we investigated whether binding of CTLA4 affects the differentiation of monocytes into osteoclasts in vitro and vivo. We show that CTLA-4 dose dependently inhibits RANKL- as well as TNF- mediated osteoclastogenesis in vitro without presence of T cells. Furthermore, CTLA-4 was effective to inhibit TNF-induced osteoclast formation in a non-T cell dependent TNF-induced model of arthritis as well as the formation of inflammatory bone erosion in vivo. These data suggest that CTLA-4 is an anti-osteoclastogenic molecule, which directly binds osteoclast precursor cells and inhibits their differentiation. These findings are an attractive explanation for the anti-erosive effect of abatacept, a CTLA-4-Ig fusion protein used for the treatment of RA.

                    • arthritis
                    • ctla-4
                    • erosion
                    • osteoclast
                    • rankl

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