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Reversible depletion of synovial lining cells after intra-articular treatment with liposome-encapsulated dichloromethylene diphosphonate

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Summary

We studied the depletion and repopulation of synovial lining cells in mice. A single intra-articular injection of liposomes encapsulating the drug dichloromethylene diphosphonate (CL2MDP) in the mouse knee joint caused selective elimination of synovial lining cells. Depletion of cells occurred within a few days as evidenced by light microscopic, electronmicroscopic and immunohistochemical studies. Maximal depletion was seen on day 7. Repopulation was observed in the following weeks, starting at the bone side of the joint. Until day 30, full recovery (60% recovery) was not observed in the lining lying adjacent to the dermis. Side effects on cartilage metabolism, such as inhibition of proteoglycan synthesis or degradation of proteoglycans from the matrix was minor but significant, 1 and 2 days after liposome treatment but thereafter full recovery was observed. Selective elimination of lining cells from the joint enabled us to study the in vivo role of these cells in the onset and subsequent pathology of experimental arthritis. An immune-complex-mediated experimental arthritis elicited in lining cell depleted joints that had received CL2MDP-liposomes 7 days earlier prevented inflammation as compared to controls.

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Authors and Affiliations

  1. Department of Rheumatology, University Hospital St. Radboud, Nijmegen, The Netherlands

    P. L. E. M. van Lent, L. van den Bersselaar, A. E. M. van den Hoek, L. B. A. van de Putte & W. B. van den Berg

  2. Department of Histology, Free University, Amsterdam, The Netherlands

    M. van de Ende, C. D. Dijkstra & N. van Rooijen

Authors
  1. P. L. E. M. van Lent
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  2. L. van den Bersselaar
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  3. A. E. M. van den Hoek
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  4. M. van de Ende
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  5. C. D. Dijkstra
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  6. N. van Rooijen
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  7. L. B. A. van de Putte
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  8. W. B. van den Berg
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van Lent, P.L.E.M., van den Bersselaar, L., van den Hoek, A.E.M. et al. Reversible depletion of synovial lining cells after intra-articular treatment with liposome-encapsulated dichloromethylene diphosphonate. Rheumatol Int 13, 21–30 (1993). https://doi.org/10.1007/BF00290330

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  • DOI: https://doi.org/10.1007/BF00290330

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