期刊
出版社
ELSEVIER
DOI: 10.1016/j.msec.2021.112234
关键词
Osteoarthritis (OA); Chondroitin sulfate (CS) E oligosaccharide; Complement system; Complement C5; Membrane-attack complex (MAC)
资金
- National Natural Science Foundation of China (NSFC) [81703403]
- China-Australia Centre for Health Sciences Research (CACHSR) [2019GJ03]
- General Financial Grant from China Postdoctoral Science Foundation [2017M622224]
- Shandong Province Postdoctoral Innovation Project [201701009]
- Fundamental Research Funds of Shandong University [2019GN092]
- Future Scholar Program of Shandong University
The study identified chondroitin sulfate E disaccharide as a potential anti-inflammatory agent for treating osteoarthritis through regulating the complement system. This discovery not only provides a new strategy for OA treatment and drug development, but also offers a promising C5 target therapy for other associated diseases.
Osteoarthritis (OA) is a degenerative joint disease which is highly prevalent worldwide. However, no therapy for blocking OA pathogenesis is available currently. In this study, chondroitin sulfate (CS) E oligosaccharides were prepared and we identified disaccharide as the functional unit showing the strongest anti-complement activity and screened out complement C5 as its target in the complement system. We determined that CS-E disaccharide produced anti-inflammatory effects to treat OA by regulating the complement system: it inhibited the formation of complement-dependent complexes such as the membrane-attack complex (MAC) by targeting C5 and suppressed MAC-induced protein expression and the activation of downstream MAPK and NF-kappa B signaling pathways accordingly. By identifying CS-E disaccharide which could be regarded as a complement regulator or inhibitor exhibiting high anti-complement activity and revealing its OA-alleviating mechanism, this study not only provides a new strategy for OA treatment and drug development, but also potentially offers a promising C5 target therapy for other associated diseases.
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