Novel transdermal photodynamic therapy using ATX-S10.Na(II) induces apoptosis of synovial fibroblasts and ameliorates collagen antibody-induced arthritis in mice.
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.
Miyazawa
S
S
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 University Hospital, Japan.
Nishida
K
K
Komiyama
T
T
Nakae
Y
Y
Takeda
K
K
Yorimitsu
M
M
Kitamura
A
A
Kunisada
T
T
Ohtsuka
A
A
Inoue
H
H
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000473:pathology; D002478:Cells, Cultured; D005347:Fibroblasts / Q000187:drug effects*; D006801:Humans; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000494:pharmacology*; D011166:Porphyrins / Q000494:pharmacology*; D011897:Random Allocation; D013582:Synovial Fluid / Q000166:cytology
C115550:ATX-S10; D017319:Photosensitizing Agents; D011166:Porphyrins