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Chondroitin Sulfate in USA Dietary Supplements in Comparison to Pharma Grade Products: Analytical Fingerprint and Potential Anti-Inflammatory Effect on Human Osteoartritic Chondrocytes and Synoviocytes.

ABSTRACT: The biological activity of chondroitin sulfate (CS) and glucosamine (GlcN) food supplements (FS), sold in USA against osteoarthritis, might depend on the effective CS and GlcN contents and on the CS structural characteristics. In this paper three USA FS were compared to two pharmaceutical products (Ph). Analyses performed by HPAE-PAD, by HPCE and by SEC-TDA revealed that the CS and GlcN titers were up to -68.8% lower than the contents declared on the labels and that CS of mixed animal origin and variable molecular weights was present together with undesired keratan sulfate. Simulated gastric and intestinal digestions were performed in vitro to evaluate the real CS amount that may reach the gut as biopolymer. Chondrocytes and synoviocytes primary cells derived from human pathological joints were used to assess: cell viability, modulation of the NF-κB, quantification of cartilage oligomeric matrix protein (COMP-2), hyaluronate synthase enzyme (HAS-1), pentraxin (PTX-3) and the secreted IL-6 and IL-8 to assess inflammation. Of the three FS tested only one (US FS1) enhanced chondrocytes viability, while all of them supported synoviocytes growth. Although US FS1 proved to be less effective than Ph as it reduced NF-kB, it could not down-regulate COMP-2; HAS-1 was up-regulated but with a lower efficacy. Inflammatory cytokines were markedly reduced by Ph while a slight decrease was only found for US-FS1.

SUBMITTER: Stellavato A

PROVIDER: S-EPMC8156081 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:INTRODUCTION:Chondroitin sulfate (CS) and glucosamine sulfate (GS) are symptomatic slow-acting drugs for osteoarthritis (OA) widely used in clinic. Despite their widespread use, knowledge of the specific molecular mechanisms of their action is limited. The aim of this work is to explore the utility of a pharmacoproteomic approach for the identification of specific molecules involved in the pharmacological effect of GS and CS. METHODS:Chondrocytes obtained from three healthy donors were treated with GS 10 mM and/or CS 200 ?g/mL, and then stimulated with interleukin-1? (IL-1?) 10 ng/mL. Whole cell proteins were isolated 24 hours later and resolved by two-dimensional electrophoresis. The gels were stained with SYPRORuby. Modulated proteins were identified by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF/TOF) mass spectrometry. Real-time PCR and Western blot analyses were performed to validate our results. RESULTS:A total of 31 different proteins were altered by GS or/and CS treatment when compared to control. Regarding their predicted biological function, 35% of the proteins modulated by GS are involved in signal transduction pathways, 15% in redox and stress response, and 25% in protein synthesis and folding processes. Interestingly, CS affects mainly energy production (31%) and metabolic pathways (13%), decreasing the expression levels of ten proteins. The chaperone GRP78 was found to be remarkably increased by GS alone and in combination with CS, a fact that unveils a putative mechanism for the reported anti-inflammatory effect of GS in OA. On the other hand, the antioxidant enzyme superoxide dismutase 2 (SOD2) was significantly decreased by both drugs and synergistically by their combination, thus suggesting a drug-induced decrease of the oxidative stress caused by IL-1? in chondrocytes. CONCLUSIONS:CS and GS differentially modulate the proteomic profile of human chondrocytes. This pharmacoproteomic approach unravels the complex intracellular mechanisms that are modulated by these drugs on IL1?-stimulated human articular chondrocytes.

Project description:INTRODUCTION:The recent CONCEPT study showed that 800 mg/day of pharmaceutical-grade chondroitin sulfate (CS) was superior to placebo and similar to celecoxib in reducing pain and improving function over 6 months in patients with symptomatic knee osteoarthritis (OA). We investigate, in the present study, whether a responder profile to CS could be defined (i.e., to determine a patient's profile with the best response to treatment). METHODS:Subjects from the CS group of the CONCEPT study were included in the present analysis. Within the CS group, various subgroups were created on the basis of different categories of age, sex, body mass index, Kellgren and Lawrence grade, age since the beginning of OA, and baseline level of pain (i.e., VAS) or function (i.e., Lequesne index). The nonparametric Kruskal-Wallis (KW) test was applied to compare the VAS pain/Lequesne index evolutions between the subgroups, and the Dwass, Steel, Critchlow, Fligner (DSCF) procedure was used to compute multiple comparisons. The impact of various covariates on the VAS pain/Lequesne index evolution was assessed by means of multiple regression. RESULTS:Across all analyses, the probability of response to CS treatment was significantly associated with the duration between the date of diagnosis and the initiation of treatment. In other words, the shorter the interval between the diagnosis and the beginning of the treatment, the higher the response for both pain and function, particularly for patients with a duration of less than 5 years compared to patients with a duration of 10 years or more. No other criteria were found to be consistently associated with the response to CS treatment. CONCLUSION:The treatment of OA with CS has the highest chance of success if administered in the early stage of the disease. Further research with other clinical outcomes should be carried out prior to widespread application of these findings. TRIAL REGISTRATION:ClinicalTrials.gov identifier, NCT03200288.

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Chondroitin Sulfate in USA Dietary Supplements in Comparison to Pharma Grade Products: Analytical Fingerprint and Potential Anti-Inflammatory Effect on Human Osteoartritic Chondrocytes and Synoviocytes.

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