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

Li, Xiang; Tang, Xiaonan; Wang, Yufei; Chai, Chang-Wei; Zhao, Zhehui; Zhang, Haijing; Peng, Ying; Wu, Li‐Wei

doi:10.3389/fphar.2021.655101

Cited by 6 publications

(7 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…By stimulating the synthesis of important components of healthy cartilage and limiting the activity of inflammatory mediators and signaling, chondroitin sulfate may have a role in protecting healthy cartilage from degeneration. However, the anti-inflammatory properties of CS are still under investigation, although the results from newer studies on this matter have been promising [64][65][66][67][68].…”

Section: Discussionmentioning

confidence: 99%

Chondroitin Sulfate Supplements for Osteoarthritis: A Critical Review

Brito¹,

Costa²,

Dias³

et al. 2023

Cureus

View full text Add to dashboard Cite

Over the years, chondroitin sulfate (CS) has been used as a slow-acting drug for the treatment of osteoarthritis, for the reduction of pain and improvement of function, and for its disease-modifying properties by limiting cartilage volume loss and joint space narrowing progression. However, there have been inconsistencies in published trials regarding clinical efficacy, with reports of a lack of significant effects compared to placebo. The therapeutic effects of chondroitin sulfate may depend on many variables, such as the source of origin, purity, and contamination with by-products. Another source of confusion may be related to the fact that CS is commonly combined with glucosamine, which makes it challenging to isolate the specific contribution of chondroitin to the therapeutic outcome. This is aggravated by the fact that CS supplements, used in many countries, are not regulated, and labels wrongly claim high levels of purity. Many of these inferior CS products may have been used in clinical trials, which may have had limited but significant results. This has led to recent recommendations to opt for higher-purity pharmacologic-grade CS for the treatment of OA. This article aims to provide an up-to-date view of the current literature regarding the biological effects and efficacy of CS and discusses the quality of available chondroitin sulfate supplements and the current direction in CS investigation. This review concludes that pharmacologic-grade CS supplements may have clinically significant benefits when properly standardized; however, high-quality evidence from properly designed clinical trials is still needed to draw definitive conclusions about clinical efficacy in osteoarthritis.

show abstract

Section: Discussionmentioning

confidence: 99%

Chondroitin Sulfate Supplements for Osteoarthritis: A Critical Review

Brito¹,

Costa²,

Dias³

et al. 2023

Cureus

View full text Add to dashboard Cite

show abstract

“…Overexpression of miR-496 in RA-FLS may inhibit cell proliferation by inactivating the NF-κB pathway (Xing et al, 2021). CS-semi5, a semisynthetic chondroitin sulfate, may effectively improve synovial inflammation, and cartilage erosion in RA through NF-κB deactivation (Li et al, 2021). Hence, the intrinsic relationship between NF-κB pathway and RA needs to be further studied in the future.…”

Section: Discussionmentioning

confidence: 99%

Identification of Tissue-Specific Expressed Hub Genes and Potential Drugs in Rheumatoid Arthritis Using Bioinformatics Analysis

et al. 2022

View full text Add to dashboard Cite

Background: Rheumatoid arthritis (RA) is a common autoimmune disease characterized by progressive, destructive polyarthritis. However, the cause and underlying molecular events of RA are not clear. Here, we applied integrated bioinformatics to identify tissue-specific expressed hub genes involved in RA and reveal potential targeted drugs.Methods: Three expression profiles of human microarray datasets involving fibroblast-like synoviocytes (FLS) were downloaded from the Gene Expression Omnibus (GEO) database, the differentially expressed mRNAs (DEGs), miRNAs (DEMs), and lncRNAs (DELs) between normal and RA synovial samples were screened using GEO2R tool. BioGPS was used to identified tissue-specific expressed genes. Functional and pathway enrichment analyses were performed for common DEGs using the DAVID database, and the protein-protein interaction (PPI) network of common DEGs was constructed to recognize hub genes by the STRING database. Based on receiver operating characteristic (ROC) curve, we further investigated the prognostic values of tissue-specific expressed hub genes in RA patients. Connectivity Map (CMap) was run to identify novel anti-RA potential drugs. The DEM–DEG pairs and ceRNA network containing key DEMs were established by Cytoscape.Results: We obtain a total of 418 DEGs, 23 DEMs and 49 DELs. 64 DEGs were verified as tissue-specific expressed genes, most derive from the hematologic/immune system (20/64, 31.25%). GO term and KEGG pathway enrichment analysis showed that DEGs focused primarily on immune-related biological process and NF-κB pathway. 10 hub genes were generated via using MCODE plugin. Among them, SPAG5, CUX2, and THEMIS2 were identified as tissue-specific expressed hub genes, these 3 tissue-specific expressed hub genes have superior diagnostic value in the RA samples compared with osteoarthritis (OA) samples. 5 compounds (troleandomycin, levodopa, trichostatin A, LY-294002, and levamisole) rank among the top five in connectivity score. In addition, 5 miRNAs were identified to be key DEMs, the lncRNA–miRNA–mRNA network with five key DEMs was formed. The networks containing tissue-specific expressed hub genes are as follows: ARAP1-AS2/miR-20b-3p/TRIM3, ARAP1-AS2/miR-30c-3p/FRZB.Conclusion: This study indicates that screening for identify tissue-specific expressed hub genes and ceRNA network in RA using integrated bioinformatics analyses could help us understand the mechanism of development of RA. Besides, SPAG5 and THEMIS2 might be candidate biomarkers for diagnosis of RA. LY-294002, trichostatin A, and troleandomycin may be potential drugs for RA.

show abstract

“…Finally, 4 μm slices were sectioned and stained with hematoxylin-eosin (H&E) for histopathological analysis and examined using light microscopy. The severity of arthritis in the joint was scored from 0 to 3 according to inflammatory cell infiltration, Pannus formation, synovial hyperplasia, destruction of articular cartilage and bone, and the total score of each mouse was calculated [ 15 ].…”

Section: Methodsmentioning

confidence: 99%

Combined treatment with glucosamine and chondroitin sulfate improves rheumatoid arthritis in rats by regulating the gut microbiota

Wang

Liu

et al. 2023

Nutr Metab (Lond)

View full text Add to dashboard Cite

Background To investigate the ameliorative effects of glucosamine (GS), chondroitin sulphate (CS) and glucosamine plus chondroitin sulphate (GC) on rheumatoid arthritis (RA) in rats, and to explore the mechanism of GS, CS and GC in improving RA based on the gut microbiota. Methods RA rat models were effectively developed 14 days after CFA injection, and then garaged with GS, CS and GC. Body weight and paw volume of rats were monitored at multiple time points at the beginning of CFA injection. Until D36, serum and ankle tissue specimens were used to measure levels of circulating inflammatory factors (TNF-α, IL-1β, MMP-3, NO and PGE2) and local inflammatory indicators (TLR-4 and NF-κB). On D18, D25, and D36, intergroup gut microbiota was compared using 16S rRNA gene sequencing and bioinformatics analysis. We also performed the correlation analysis of gut bacteria, joint swelling and inflammatory indicators. Results GC, rather than GS and CS, could reduce right paw volumes, levels of TLR-4 and NF-κB in synovial tissues. In addition, enriched genera in RA model rats screened out by LEfSe analysis could be inhibited by GC intervention, including potential LPS-producing bacteria (Enterobacter, Bacteroides, Erysipelotrichaceae_unclassified and Erysipelotrichaceae_uncultured) and some other opportunistic pathogens (Esherichia_Shigella, Nosocomiicoccus, NK4A214_group, Odoribacter, Corynebacterium and Candidatus_Saccharimonas.etc.) that positively correlated with pro-inflammatory cytokines, right paw volume, and pathology scores. Furthermore, the gut microbiota dysbiosis was observed to recover before alleviating joint swelling after interventions. Conclusions GC could inhibit potential LPS-producing bacteria and the activation of TLR-4/NF-κB pathway in RA rats, thus alleviating RA-induced joint injury.

show abstract

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

Cited by 6 publications

References 58 publications

Chondroitin Sulfate Supplements for Osteoarthritis: A Critical Review

Chondroitin Sulfate Supplements for Osteoarthritis: A Critical Review

Identification of Tissue-Specific Expressed Hub Genes and Potential Drugs in Rheumatoid Arthritis Using Bioinformatics Analysis

Combined treatment with glucosamine and chondroitin sulfate improves rheumatoid arthritis in rats by regulating the gut microbiota

Contact Info

Product

Resources

About