Abstract
Osteoclasts are multinucleated giant cells of macrophage/monocyte lineage, and cell differentiation with the upregulation of osteoclast-related proteins is believed to play a major role in the destruction of the joints in the course of rheumatoid arthritis (RA). Pro-inflammatory cytokines, such as interleukin-17A (IL-17A) and macrophage colony-stimulating factor (M-CSF), can be overexpressed in RA and lead to osteoclastogenesis. In a previous study, we found that cultured-type soft coral-derived excavatolide B (Exc-B) exhibited anti-inflammatory properties. In the present study, we thus aimed to evaluate the anti-arthritic activity of Exc-B in in vitro and in vivo models. The results demonstrated that Exc-B inhibits LPS-induced multinucleated cell and actin ring formation, as well as TRAP, MMP-9, and cathepsin K expression. Additionally, Exc-B significantly attenuated the characteristics of RA in adjuvant (AIA) and type II collagen-induced arthritis (CIA) in rats. Moreover, Exc-B improved histopathological features, and reduced the number of TRAP-positive multinucleated cells in the in vivo AIA and CIA models. Immunohistochemical analysis showed that Exc-B attenuated the protein expression of cathepsin K, MMP-2, MMP-9, CD11b, and NFATc1 in ankle tissues of AIA and CIA rats. Level of interleukin-17A and macrophage colony-stimulating factor were also decreased by Exc-B. These findings strongly suggest that Exc-B could be of potential use as a therapeutic agent by inhibiting osteoclast differentiation in arthritis. Moreover, this study also illustrates the use of the anti-inflammatory marine compound, Exc-B, as a potential therapeutic strategy for RA.
Highlights
Rheumatoid arthritis (RA) is an autoimmune-mediated inflammatory disease characterized by synovial inflammation, as well as joint damage, cartilage destruction, and bone erosion with osteoclast activation [1]
We found that excavatolide B (Exc-B) could inhibit inducible nitric oxide synthase and cyclooxygenase-2 (COX-2) gene and protein expression in LPS-induced RAW 264.7 cells in an in vitro model
We found that Exc-B significantly reduced the level of IL-17A in the serum of adjuvant-induced arthritis (AIA)- and collagen-induced arthritis (CIA)-rats
Summary
Rheumatoid arthritis (RA) is an autoimmune-mediated inflammatory disease characterized by synovial inflammation, as well as joint damage, cartilage destruction, and bone erosion with osteoclast activation [1]. The immune system will attack the joint tissue, leading to redness, oedema, and ankyloses [4,5]. Pannus formation leads to an increase in the number of blood vessels by angiogenesis and greater immune cells clustering and infiltration in the synovial tissue [8]. The pannus can cover the cartilage and bone surface and cause joint damage involving complex immune and inflammatory responses by different infiltrating cells [8]. The up-regulation of pro-inflammatory cytokines, proteases, and matrix metalloproteinases, released from infiltrating cells of the pannus, can induce changes in chondrocyte metabolism and matrix degradation, leading to cartilage damage and bone erosion [9]. For more effective treatment of RA, antagonists of tumour necrosis factor alpha (TNF-α), interleukin 1 (IL-1), interleukin
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
