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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-κB 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., (Copyright © 2021 Elsevier B.V. All rights reserved.)

We have previously reported an application of lower range of molecular weight of xanthan gum (LRWXG) for inhibiting cartilage matrix destruction and preventing mitochondrial damage in rabbit osteoarthritis (OA) model. However, whether LRWXG exerts its anti-OA activity through intrinsic bax-mitochondria cytochrome c-caspase signaling pathway in OA still requires further study. To address this problem, the OA model was induced by anterior cruciate ligament transection (ACLT) in rabbit and then treated with LRWXG. The results showed that LRWXG could inhibit the loss of collagen in cartilage matrix, protect trabecular bone in subchondral, decrease the apoptosis of chondrocytes, down-regulate the expressions of active caspase-9, active caspase-3 and bax, and up-regulate the expression of bcl-2. In addition, LRWXG could up-regulate the expression of cyt-c in mitochondria, while down-regulate the expression of cyt-c in cytoplasm. These findings show that LRWXG inhibits cartilage degradation via an intrinsic bax-mitochondria cytochrome c-caspase pathway in OA., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The polysaccharides used in the treatment of osteoarthritis (OA) mainly include sodium hyaluronate, chondroitin sulfate, chitosan, xanthan gum, Low molecular weight heparin, alginate and other polysaccharides. This review summarizes the recent advances in the chemistry and biological activities of polysaccharides for the treatment of OA., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Osteoarthritis (OA) is one of the most common chronic diseases and characterized by degradation of articular cartilage. We have previously reported xanthan gum (XG) injection preparation with high molecular weights (Mw) in ranging from 3×10 6 Da to 5×10 6 Da (HM-XG) could enhance the viscosity of synovial fluid, protect joint cartilage in rabbit, and the therapeutical effect has no significance difference with an existing clinical medication (sodium hyaluronate, SH) at the same injection frequency (once weekly for 5 weeks). Herein, we prepared a XG injection preparation with a low Mw (LM-XG) in ranging from 1×10 6 Da to 1.5×10 6 Da, and evaluated the therapeutical effect for OA therapy at once every 2 weeks for 5 weeks with an SH at once weekly for 5 weeks as reference. The model of OA was induced using anterior cruciate ligament transection (ACLT) in a rabbit in vivo and also using sodium nitroprusside (SNP) in cell culture in vitro. The results showed that LW-XG could also protect cartilage from damage, decrease the concentration of nitric oxide (NO) in synovial fluid and reverse the amplification of the knee joint width similar to HM-XG as our previously reported. At the cellular level, LW-XG promotes proliferation while decreases apoptosis of chondrocytes. Mechanistically at the molecular level, these effects are elicited via down-regulation of the protein levels of caspase-3 and bax and up-regulation of the protein levels of bcl-2 in cartilage in both in vivo and in vitro. These results showed that LW-XG maybe become an excellent candidate long-acting drug for treating OA., (Copyright © 2017. Published by Elsevier Ltd.)

Chondroitin sulfate (CS) plays important roles in the complement system. However, the CS structure is complicated due to different sources and the number and positions of sulfate groups. The objective of this study was to prepare different low molecular weight chondroitin sulfates (LMWCSs) and to investigate the biological activity in anti-complement capacity. A series of LMWCSs was prepared from different sources and characterized by ultraviolet-visible (UV) spectroscopy, high-performance liquid chromatography (HPLC), size exclusion chromatography-multiangle laser light scattering (SEC-MALLS) and nuclear magnetic resonance (NMR) spectroscopy. Hemolytic, anti-complement 3 deposition capacity and cell viability assays were carried out to investigate the biological activities in vitro. The results showed that LMWCS prepared from shark cartilage with the oxidative degradation method (LMWCS-S-O) had the best anti-complement capacity. LMWCS-S-O could inhibit the alternative pathway of the complement system and protect chondrocytes from cell death. The attenuating effect of LMWCS-S-O on Osteoarthritis (OA) was investigated by destabilization of the medial meniscus (DMM) model in vivo. Functional wind-up, histological and C5b-9 analyses were used to evaluate the treatment effect on the OA model. In vivo results showed that LMWCS-S-O could attenuate OA. LMWCS-S-O with a high content of ΔDi-2,6diS and ΔDi-6S could be used for attenuating OA through regulating the complement system., Competing Interests: The authors declare no conflict of interest.

The objective of this study was to evaluate the alleviative effect of intra-articular (IA) injection of xanthan gum (XG) on pain and cartilage degradation in a model of monosodium iodoacetate (MIA)-induced knee osteoarthritis (OA). The rheological study and hyaluronidase (HAse) degradation analysis of XG injection were presented. The effect of pain relief was determined by measurements of paw withdrawal threshold and weight bearing by hind limbs. The protective effect on the cartilage was evaluated by gross morphological observation and histological evaluation of knee joints. The effect was investigated in two protocols: a therapeutic treatment protocol, and a prophylactic treatment protocol. Our results showed that HAse had no effect on the rheological properties of XG injection. Local XG administration in both protocols could reduce OA pain and alleviate the joint cartilage degradation induced by MIA. IA injection of XG might be an effective method for OA treatment in human., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Complement system is composed of over 30 proteins and it plays important roles in self-defence and inflammation. There are three activation pathways, including classical pathway, alternative pathway and lectin pathway, in complement system, and they are associated with many diseases such as osteoarthritis and age-related macular degeneration. Modulation of the complement system may be a promising strategy in the treatment of related diseases. Glycosaminoglycans are anionic linear polysaccharides without branches. They are one kind of multi-functional macromolecules which have great potential in regulating complement system. This review is organized around two aspects between the introduction of complement system and the interaction of glycosaminoglycans with complement system. Three complement activation pathways and the biological significance were introduced first. Then functional analysis methods were compared to provide a strategy for potential glycosaminoglycans screen. Finally, the roles of glycosaminoglycans played in the complement system were summed up. [ABSTRACT FROM AUTHOR]

Abstract: This study was conducted to evaluate the protective effect of intra-articular (IA) injection of xanthan gum (XG) on articular cartilage in the papain-induced osteoarthritis (OA) model. The purified XG and injection were prepared and their qualities were evaluated. The rabbit knee OA model was induced through IA injection of papain and the protective effect on articular cartilage was evaluated through recording the width of knee joint, performing the morphological observation and histological evaluation of articular cartilage and synovium, measuring the sulphated glycosaminoglycans (GAGs) in cartilage. Our results showed that XG injection was of high transparency, low protein and endotoxin-free. IA injection of XG could protect the joint cartilage and this was probably an effective therapeutic method of OA. [Copyright &y& Elsevier]