Imperative and effective reversion of synovial hyperplasia and cartilage destruction in rheumatoid arthritis through multiple synergistic effects of O2 and Ca2.

Abstract

Abnormal synovial hyperplasia and cartilage destruction in a joint cavity are the key causes affecting the pain and disability in rheumatoid arthritis (RA) and, unfortunately, there exists no effective treatment for them. This investigation reports an effective reversion of the above pathological characteristics in RA owing to the use of a prolonged O2/Ca2+-supporting phototherapy hydrogel. The performed in vitro and in vivo experiments exhibit that the prolonged O2-supporting not only promotes the direct cell-killing effects of singlet oxygen, but also persistently blocks the pathological feedback between the abnormal proliferation of fibroblast-like synoviocyte and the local oxygen depletion. Furthermore, the Ca2+, which is the other decomposition product of the O2 donor, induces mitochondrial Ca2+ overload and endoplasmic reticulum Ca2+ disorder and triggers Ca2+-associated apoptosis and immunogenic cell death. In addition to these multiple synergistic effects on synovial hyperplasia, the prolonged Ca2+ support can also induce the regeneration of cartilage in RA affected joints. The present study may thus provide an effective therapeutic strategy for the prevention and reversion of joint lesions and the accompanying arthralgia and deformity in RA.