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Novel transdermal photodynamic therapy using ATX-S10·Na(II) induces apoptosis of synovial fibroblasts and ameliorates collagen antibody-induced arthritis in mice

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Abstract

We aimed to test the effect of transdermal photodynamic therapy (PDT) on synovial proliferation in vitro and in vivo, using a novel photosensitizer, ATX-S10·Na(II). Synovial fibroblasts were obtained from patients with RA (RASF). Cell viability with or without PDT was determined by MTT assay. Cell morphology was examined by light and transmission electron microscopy. DNA fragmentation was labeled by TUNEL stain. Collagen antibody-induced arthritis (CAIA) was induced in DBA/1 mice, and the effects of transdermal PDT were evaluated by clinical and histological examination. PDT showed drug concentration-dependent and laser dose-dependent cytotoxicity on RASF. TUNEL stain and TEM study revealed the induction of apoptotic cell death of RASF. Transdermal PDT significantly reduced clinical arthritis and synovial inflammation in this model of arthritis. These results suggest that transdermal PDT using ATX-S10·Na(II) might be a novel less invasive treatment strategy for small joint arthritis and tenosynovitis.

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References

  1. Gardner DL (1992) Rheumatoid arthritis: cell and tissue pathology. In: Pathological basis of the connective tissue diseases. Edward Arnold, London, pp 444–526

  2. Weitoft T, Uddenfeldt P (2000) Importance of synovial fluid aspiration when injecting intra-articular corticosteroids. Ann Rheum Dis 59:233–235

    Article  PubMed  CAS  Google Scholar 

  3. Proudman SM, Conaghan PG, Richardson C, Griffiths B, Green MJ, McGonagle D, Wakefield RJ, Reece RJ, Miles S, Adebajo A, Gough A, Helliwell P, Martin M, Huston G, Pease C, Veale DJ, Isaacs J, van der Heijde DM, Erery P (2000) Treatment of poor-prognosis early rheumatoid arthritis. Arthritis Rheum 43:1809–1819

    Article  PubMed  CAS  Google Scholar 

  4. Conaghan PG, O’Connor P, McGonagle D, Astin P, Wakefield RJ, Gibbon WW, Quinn M, Karim Z, Green MJ, Proudman S, Isaacs J, Emery P (2003) Elucidation of the relationship between synovitis and bone damage. Arthritis Rheum 48:64–71

    Article  PubMed  Google Scholar 

  5. Tanaka N, Sakahashi H, Sato E, Ishii S (2002) Immunohistological indication for arthroscopic synovectomy in rheumatoid knees: analysis of synovial samples obtained by needle arthroscopy. Clin Rheumatol 21:46–51

    Article  PubMed  CAS  Google Scholar 

  6. Parikh JR, Houpt JB, Jacobs S, Fernandes BJ (1993) Charcot’s arthropathy of the shoulder following intraarticular corticosteroid injections. J Rheumatol 20:885–887

    PubMed  CAS  Google Scholar 

  7. Moore GF (2005) Arthrocentesis technique and intraarticular therapy. In:Therapeutic approaches in the rheumatic diseases. Arthritis and Allied Conditions A Textbook of Rheumatology, Lippincott Williams and Wilkins, Philadelphia, pp 775–786

  8. Kulkarni A, Brooks S, Pynsent PB (2003) Is bilateral knee arthroscopy suitable as a day-case procedure? Knee 10:287–289

    Article  PubMed  CAS  Google Scholar 

  9. Obana A, Gohto Y (2002) Scanning laser system for photodynamic therapy of choroidal neovascularization. Lasers Surg Med 30:370–375

    Article  PubMed  Google Scholar 

  10. Hikichi T, Mori F, Nakajima S, Takamiya TA, Takeda M, Sasaki M, Horikawa Y, Yoshida A (2001) Dynamic observation of selective accumulation of a photosensitizer and its photodynamic effects in rat experimental choroidal neovascularization. Retina 21:126–131

    Article  PubMed  CAS  Google Scholar 

  11. Tang G, Hyman S, Schneider JH Jr, Giannotta SL (1993) Application of photodynamic therapy to the treatment of atherosclerotic plaques. Neurosurgery 32:438–443

    Article  PubMed  CAS  Google Scholar 

  12. Hsiang YN, Crespo MT, Machan LS, Bower RD, Todd ME (1994) Photodynamic therapy for atherosclerotic stenosis in Yucatan miniswine. Can J Surg 37:148–152

    PubMed  CAS  Google Scholar 

  13. Igarashi A, Konno H, Tanaka T, Nakamura S, Sadzuka Y, Hirano T, Fujise Y (2003) Liposomal photofrin enhances therapeutic efficacy of photodynamic therapy against the human gastric cancer. Toxicol Lett 145:133–141

    Article  PubMed  CAS  Google Scholar 

  14. Takahira K, Sano M, Arai H, Hanai H (2004) Apoptosis of gastric cancer cell line MKN45 by photodynamic treatment with photofrin. Lasers Med Sci 19:89–94

    Article  PubMed  Google Scholar 

  15. Hopfner M, Maaser K, Theiss A, Lenz M, Sutter AP, Kashtan H, von Lampe B, Riecken EO, Zeitz M, Scherubl H (2003) Hypericin activated by an incoherent light source has photodynamic effects on esophageal cancer cells. Int J Colorectal Dis 18:239–247

    PubMed  CAS  Google Scholar 

  16. Litle VR, Luketich JD, Christie NA, Buenaventura PO, Alvelo-Rivera M, McCaughan JS, Nguyen NT, Fernando HC (2003) Photodynamic therapy as palliation for esophageal cancer: experience in 215 patients. Ann Thorac Surg 76:1687–1692

    Article  PubMed  Google Scholar 

  17. Kato H, Furukawa K, Sato M, Okunata T, Kusunoki Y, Kawahara M, Fukuoka M, Miyazawa T, Yana T, Matsui K, Shiraishi T, Horinouchi H (2003) Phase II clinical study of photodynamic therapy using mono-l-aspartyl chlorin e6 and diode laser for early superficial squamous cell carcinoma of the lung. Lung Cancer 42:103–111

    Article  PubMed  Google Scholar 

  18. Okumura T, Kato H, Tsutsui H, Ishizumi T, Ichinose S, Kuroiwa Y (2004) Photodynamic therapy for peripheral lung cancer. Lung Cancer 43:77–82

    Article  Google Scholar 

  19. Ahn WS, Bae SM, Huh SW, Lee JM, Namkoong SE, Han SJ, Kim CK, Kim JK Kim YW (2004) Necrosis-like death with plasma membrane damage against cervical cancer cells by photodynamic therapy. Int J Gynecol Cancer 14:475–482

    Article  PubMed  CAS  Google Scholar 

  20. Beischer AD, Bhathal P, Steiger R, Penn D, Stylli S (2002) Synovial ablation in a rabbit rheumatoid arthritis model using photodynamic therapy. ANZ J Surg 72:517–522

    Article  PubMed  Google Scholar 

  21. Chowdhary RK, Ratkay LG, Canaan AJ, Waterfield JD, Richter AM, Levy JG (1998) Uptake of Verteporfin® by articular tissues following systematic and intra-articular administration. Biopharm Drug Dispos 19:395–400

    Article  PubMed  CAS  Google Scholar 

  22. Trauner KB, Gandour-Edwards R, Bamberg M, Shortkroff S, Sledge C, Hasan T (1998) Photodynamic synovectomy using benzoporphyrin derivative in an antigen-induced arthritis model for rheumatoid arthritis. Photochem Photobiol 67:133–139

    PubMed  CAS  Google Scholar 

  23. Ratkay LG, Chowdhary RK, Iamaroon A, Richter AM, Neyndorff HC, Keystone EC, Waterfield JD, Levy JG (1998) Amelioration of antigen-induced arthritis in rabbits by induction of apoptosis of inflammatory cells with local application of transdermal photodynamic therapy. Arthritis Rheum 41:525–534

    Article  PubMed  CAS  Google Scholar 

  24. Chowdhary RK, Sharif I, Chansarkar N, Dolphin D, Ratkay L, Delaney S, Meadows H (2003) Correlation of photosensitizer delivery to lipoproteins and efficacy in tumor and arthritis mouse models; comparison of lipid-based and Pluronic P123 formulations. J Pharm Pharm Sci 6:198–204

    PubMed  CAS  Google Scholar 

  25. Hendrich C, Huttmann G, Lehnert C, Diddens H, Siebert WE (1997) Photodynamic laser therapy for rheumatoid arthritis; cell culture studies and animal experiments. Knee Surg Sports Traumatol Arthrosc 5:58–63

    Article  PubMed  CAS  Google Scholar 

  26. Trauner KB, Hasan T (1996) photodynamic treatment of rheumatoid and inflammatory arthritis. Photochem Photobiol 64:740–750

    Article  PubMed  CAS  Google Scholar 

  27. Wagnieres G, Hadjur C, Grosjean P, Braichotte D, Savary JF, Monnier P, van den Bergh H (1998) Clinical evaluation of the cutaneous phototoxicity of 5,10, 15, 20-tetra (m-hydroxyphenyl) chlorin. Photochem Photobiol 68:382–387

    Article  PubMed  CAS  Google Scholar 

  28. Tajiri H, Yokoyama K, Boku N, Ohtsu A, Fujii T, Yoshida S, Sato T, Hakamata K, Hayashi K, Sakata I (1997) Fluoresent diagnosis of experimental gastric cancer using a tumor-localizing photosensitizer. Cancer Lett 111:215–220

    Article  PubMed  CAS  Google Scholar 

  29. Nakajima S, Sakata I, Hirano T, Takemura T (1998) Therapeutic effect of intersitial photodynamic therapy using ATX-S10 (Na) and diode laser on radio-resistant SCCVII tumors of C3H/He mice. Anticancer Drugs 9:539–543

    Article  PubMed  CAS  Google Scholar 

  30. Takahashi H, Itoh Y, Nakajima S, Sakata I, Iizuka H (2004) A novel ATX-S10 (Na) photodynamic therapy for human skin tumors and benign hyperproliferative skin. Photodermatol Photoimmunol Photomed 20:257–265

    Article  PubMed  CAS  Google Scholar 

  31. Mori M, Sakata I, Hirano T, Obana A, Nakajima S, Hikida M, Kumagai T (2000) Photodynamic therapy for experimental tumors using ATX-S10 (Na), a hydrophilic chlorin photosensitizer, and diode laser. Jpn J Cancer Res 91:753–759

    PubMed  CAS  Google Scholar 

  32. Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, Healey LA, Kaplan SR, Liang MH, Luthra HS, Medsger TA, Mitchell DM, Neustadt DH, Pinals RS, Schaller JG, Sharp JT, Wilder RL, Hunder (1988) The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 31:315–324

    Article  PubMed  CAS  Google Scholar 

  33. Morita Y, Yamamura M, Nishida K, Harada S, Okamoto H, Inoue H, Ohmoto Y, Modlin RL, Makino H (1998) Expression of interleukin-12 in synovial tissue from patients with rheumatoid arthritis. Arthritis Rheum 41:306–314

    Article  PubMed  CAS  Google Scholar 

  34. Nishida K, Furumatsu T, Takada I, Kawai A, Yoshida A, Kunisada T, Inoue H (2002) Inhibition of human chondrosarcoma cell growth via apoptosis by perioxisome proliferator-activated receptor-γ. Br J Cancer 86:1303–1309

    Article  PubMed  CAS  Google Scholar 

  35. Terato K, Hasty KA, Reife RA, Cremer MA, Kang AH Stuart JM (1992) Induction of arthritis with monoclonal antibodies to collagen. J Immunol 148:2103–2108

    PubMed  CAS  Google Scholar 

  36. Kato H, Nishida K, Yoshida A, Takada I, McCown C, Matsuo M, Murakami T, Inoue H (2003) Effect of NOS2 gene deficiency on the development of autoantibody mediated arthritis and subsequent articular cartilage degeneration. J Rheumatol 30:247–255

    PubMed  CAS  Google Scholar 

  37. Yamamoto N, Sakai F, Kon S, Morimoto J, Kimura C, Yamazaki H, Okazaki I, Seki N, Fujii T, Uede T (2003) Essential role of SLAYGLR within osteopontin in a murine model of rheumatoid arthritis. J Clin Invest 112:181–188

    PubMed  CAS  Google Scholar 

  38. Huang Y, Obana A, Gohto Y, Nakajima S (2004) Comparative study of the phototoxity of two chlorin type photosensitizers, ATX-S10 (Na) and Verteporfin, on vascular endothelial and retinal pigment epithelial cells. Laser Surg Med 34:216–226

    Article  Google Scholar 

  39. Kessel D, Luo Y, Mathieu P, Reiners JJ Jr (2000) Determination of the apoptotic response to lysosomal photodamage. Photochem Photobiol 71:196–200

    Article  PubMed  CAS  Google Scholar 

  40. Takahashi H, Itoh Y, Miyauchi Y, Nakajima S, Sakata I, Ishida-Yamamoto A, Iizuka H (2003) Activation of two caspase cascades, caspase 8/3/6 and caspase 9/3/6, during photodynamic therapy using a novel photosensitizer, ATX-S10 (Na), in normal human keratinocytes. Arch Dermatol Res 295:242–248

    Article  PubMed  CAS  Google Scholar 

  41. Mori M, Kuroda T, Obana A, Sakata I, Hirano T, Nakajima S, Hikida M, Kumagai T (2000) In vitro plasma protein binding and cellular uptake of ATX-S10 (Na), a hydrophilic chlorin photosensitizer. Jpn J Cancer Res 91:845–852

    PubMed  CAS  Google Scholar 

  42. Nagata S, Obana A, Gohto Y, Nakajima S (2003) Necrotic and apoptotic cell death of human malignant melanoma cells following photodynamic therapy using amphiphilic photosensitizer, ATX-S10 (Na). Lasers Surg Med 33:64–70

    Article  PubMed  Google Scholar 

  43. Masumoto K, Yamada I, Tanaka H, Fujise Y, Hashimoto K (2003) Tissue distribution of a new photosensitizer ATX-S10Na (II) and effect of a diode laser (670 nm) in photodynamic therapy. Lasers Med Sci 18:134–138

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

The authors thank Mrs. C. McCown for editing the manuscript. We also thank Dr. Isao Sakata, Photochemical Co. Ltd. (Okayama, Japan) for kind cooperation in preparing and providing ATX-S10·Na(II), and Hamamatsu Photonics Inc. (Hamamatsu, Japan) for providing the diode laser system.

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Authors and Affiliations

  1. Department of Orthopaedic Surgery, Science of Functional Recovery and Reconstruction, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, 700-8558, Okayama, Japan

    S. Miyazawa, K. Nishida, T. Komiyama, K. Takeda, M. Yorimitsu & A. Kitamura

  2. Department of Human Morphology, Science of Functional Recovery and Reconstruction, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, 700-8558, Okayama, Japan

    K. Nishida & A. Ohtsuka

  3. Photochemical Co. Ltd., Okayama, Japan

    Y. Nakae

  4. Department of Orthopaedic Surgery, Okayama University Hospital, Okayama, Japan

    T. Kunisada

  5. National University Corporation, Okayama University, Okayama, Japan

    H. Inoue

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  1. S. Miyazawa
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Correspondence to K. Nishida.

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Miyazawa, S., Nishida, K., Komiyama, T. et al. Novel transdermal photodynamic therapy using ATX-S10·Na(II) induces apoptosis of synovial fibroblasts and ameliorates collagen antibody-induced arthritis in mice. Rheumatol Int 26, 717–725 (2006). https://doi.org/10.1007/s00296-005-0052-9

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  • DOI: https://doi.org/10.1007/s00296-005-0052-9

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