C5a aggravates dysfunction of the articular cartilage and synovial fluid in rats with knee joint immobilization

Abstract

Degenerative alterations in articular cartilage are involved in the pathogenesis of osteoarthritis. The present study aimed to evaluate the role of complement component 5a (C5a) in osteoarthritic alterations in the articular cartilage and synovialis via a joint immobilization (IM) rat model. Rats were assigned to three groups: Control, IM and IM+anti-C5a antibody (IM+anti-C5a) groups. A terminal deoxynucleotidyl transferase dUTP nick end labeling assay and hematoxylin and eosin staining were used to evaluate the morphological alterations in the articular cartilage and synovialis. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis, immunohistochemical analysis and western blotting were used to evaluate C5a expression in the articular cartilage and synovialis. An ELISA was used to evaluate C5a-induced alterations in interleukin (IL)-1β, IL-17A and tumor necrosis factor (TNF)-α levels in the serum and joint fluid. The results demonstrated that knee joint immobilization induced destruction of knee joint synovial fluid and cartilage in the IM and IM+anti-C5a antibody groups. Immobilization significantly increased the expression levels of C5a in serum and joint fluid in the IM group. Immunohistochemistry, western blotting and RT-qPCR analysis illustrated markedly increased expression of C5a in the IM group. Immobilization markedly increased the IL-1β, IL-17A and TNF-α expression levels in the serum and joint fluid in the IM group. Anti-C5a was able to decrease immobilization-induced alterations in morphology and cytokines compared with the IM group. The expression of C5a was increased in synoviocytes and joint cartilage in the IM model. Pro-inflammatory cytokines, including TNF-α and IL-1β were released in the activated synoviocytes via the induction of C5a, suggesting that C5a serves an important role in joint inflammatory processes.

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