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

Shinichi Miyazawa, Keiichiro Nishida, T. Komiyama, Y. Nakae, K. Takeda, M. Yorimitsu, A. Kitamura, Toshiyuki Kunisada, Aiji Ohtsuka, H. Inoue

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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.

Original languageEnglish
Pages (from-to)717-725
Number of pages9
JournalRheumatology International
Volume26
Issue number8
DOIs
Publication statusPublished - Jun 2006

Fingerprint

Experimental Arthritis
Photochemotherapy
Fibroblasts
Apoptosis
Antibodies
Arthritis
In Situ Nick-End Labeling
Coloring Agents
Tenosynovitis
Inbred DBA Mouse
Photosensitizing Agents
DNA Fragmentation
Transmission Electron Microscopy
ATX S10Na(II)
Cell Survival
Lasers
Cell Death
Joints
Inflammation
Light

Keywords

  • Apoptosis
  • ATX-S10·Na(II)
  • Fibroblast
  • Photodynamic therapy
  • Rheumatoid arthritis

ASJC Scopus subject areas

  • Rheumatology

Cite this

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title = "Novel transdermal photodynamic therapy using ATX-S10·Na(II) induces apoptosis of synovial fibroblasts and ameliorates collagen antibody-induced arthritis in mice",
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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author = "Shinichi Miyazawa and Keiichiro Nishida and T. Komiyama and Y. Nakae and K. Takeda and M. Yorimitsu and A. Kitamura and Toshiyuki Kunisada and Aiji Ohtsuka and H. Inoue",
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AU - Miyazawa, Shinichi

AU - Nishida, Keiichiro

AU - Komiyama, T.

AU - Nakae, Y.

AU - Takeda, K.

AU - Yorimitsu, M.

AU - Kitamura, A.

AU - Kunisada, Toshiyuki

AU - Ohtsuka, Aiji

AU - Inoue, H.

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N2 - 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.

AB - 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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KW - Fibroblast

KW - Photodynamic therapy

KW - Rheumatoid arthritis

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