4.7 Article

CS-semi5 Inhibits NF-κB Activation to Block Synovial Inflammation, Cartilage Loss and Bone Erosion Associated With Collagen-Induced Arthritis

Journal

FRONTIERS IN PHARMACOLOGY
Volume 12, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fphar.2021.655101

Keywords

rheumatoid arthritis; synovial inflammation; cartilage erosion; bone loss; chondroitin sulfate

Funding

  1. Fundamental Research Funds for the Central Universities [3332019073]
  2. Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences

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CS-semi5 showed positive effects on collagen-induced arthritis in mice, alleviating main pathologies and reducing inflammation and bone loss through NF-kappa B deactivation. CS-semi5 treatment decreased TNF-alpha and IL-1 beta production in activated macrophages and inhibited osteoclast differentiation from macrophages. Therefore, CS-semi5 may effectively ameliorate symptoms of rheumatoid arthritis by modulating the immune pathway.
Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease that affects 1% of the population. CS-semi5 is a semisynthetic chondroitin sulfate. In this study, CS-semi5 was shown to have positive effects on a model of collagen-induced arthritis (CIA). CS-semi5 treatment had obvious effects on weight loss and paw swelling in CIA mice. Post-treatment analysis revealed that CS-semi5 alleviated three main pathologies (i.e., synovial inflammation, cartilage erosion and bone loss) in a dose-dependent manner. Further study showed that CS-semi5 could effectively reduce TNF-alpha and IL-1 beta production in activated macrophages via the NF-kappa B pathway. CS-semi5 also blocked RANKL-trigged osteoclast differentiation from macrophages. Therefore, CS-semi5 may effectively ameliorate synovial inflammation, cartilage erosion and bone loss in RA through NF-kappa B deactivation.

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