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Biomarkers, type II collagen, glucosamine and chondroitin sulfate in osteoarthritis follow-up: the "Magenta osteoarthritis study".

ABSTRACT: BACKGROUND: The purpose of the present study was to determine relationship between disease activity, systemic markers of cartilage degradation, urinary C-terminal cross-linking telopeptides of type II collagen (uCTX-II), and bone degradation, urinary C-terminal cross-linking telopeptides of type I collagen (uCTX-I), structural progression of osteoarthritis (OA) and potential therapeutic efficacy of type II collagen (COLLII) in combination with glucosamine and chondroitin sulfate (GC). MATERIALS AND METHODS: An observational retrospective study, 1-year follow-up, on 104 patients with OA (nodular osteoarthritis of the hand, erosive osteoarthritis of the hand, EOA, osteoarthritis of the knee or hip) who were treated with GC or glucosamine, chondroitin sulfate and collagen type II (GCC). The following information was collected at entry: demographics, BMI, characteristics of OA, patient global assessment (VAS), C-terminal cross-linking telopeptides of collagen types I (uCTX-I) and II (uCTX-II) and radiographs. After 6 months: VAS, uCTX-I and uCTX-II. After 1 year: VAS, uCTX-I, uCTX-II and radiographs. RESULTS: After 6 months and 1 year of treatment VAS, uCTX-I and uCTX-II mean values were significantly lower than the baseline. 57 were treated with GCC and 47 with GC. The group that received GCC showed a similar VAS mean value after 6 months and 1 year when compared with the group treated with GC. uCTX-I and uCTX-II mean level was lower in the group treated with GCC (P < 0.05). Radiological score (Kellgren and Lawrence summarized score for hands) after 1 year showed a reduced progression compared to the baseline in the hand osteoarthritis group, especially after GCC treatment (P < 0.05). Finally, uCTX-I has better correlation with radiological score and with GC in the EOA subgroup (Pearson index: R = 0.44). CONCLUSIONS: (a) uCTX-I and uCTX-II proved to be useful biomarkers in OA monitoring; (b) uCTX-I is better correlated with hand EOA and could represent a potential further marker to assess the evolution of EOA bone damage; (c) GC slow down OA progression; (d) finally COLLII could represent a further protective factor in OA cartilage.

SUBMITTER: Scarpellini M

PROVIDER: S-EPMC2656961 | biostudies-other | 2008 Jun

REPOSITORIES: biostudies-other

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Project description:OBJECTIVE:Osteoarthritis (OA) of the knee causes significant morbidity and current medical treatment is limited to symptom relief, while therapies able to slow structural damage remain elusive. This study was undertaken to evaluate the effect of glucosamine and chondroitin sulfate (CS), alone or in combination, as well as celecoxib and placebo on progressive loss of joint space width (JSW) in patients with knee OA. METHODS:A 24-month, double-blind, placebo-controlled study, conducted at 9 sites in the United States as part of the Glucosamine/Chondroitin Arthritis Intervention Trial (GAIT), enrolled 572 patients with knee OA who satisfied radiographic criteria (Kellgren/Lawrence [K/L] grade 2 or grade 3 changes and JSW of at least 2 mm at baseline). Patients with primarily lateral compartment narrowing at any time point were excluded. Patients who had been randomized to 1 of the 5 groups in the GAIT continued to receive glucosamine 500 mg 3 times daily, CS 400 mg 3 times daily, the combination of glucosamine and CS, celecoxib 200 mg daily, or placebo over 24 months. The minimum medial tibiofemoral JSW was measured at baseline, 12 months, and 24 months. The primary outcome measure was the mean change in JSW from baseline. RESULTS:The mean JSW loss at 2 years in knees with OA in the placebo group, adjusted for design and clinical factors, was 0.166 mm. No statistically significant difference in mean JSW loss was observed in any treatment group compared with the placebo group. Treatment effects on K/L grade 2 knees, but not on K/L grade 3 knees, showed a trend toward improvement relative to the placebo group. The power of the study was diminished by the limited sample size, variance of JSW measurement, and a smaller than expected loss in JSW. CONCLUSION:At 2 years, no treatment achieved a predefined threshold of clinically important difference in JSW loss as compared with placebo. However, knees with K/L grade 2 radiographic OA appeared to have the greatest potential for modification by these treatments.

Project description:ObjectivesTo compare the efficacy and safety of chondroitin sulfate plus glucosamine hydrochloride (CS+GH) versus celecoxib in patients with knee osteoarthritis and severe pain.MethodsDouble-blind Multicentre Osteoarthritis interVEntion trial with SYSADOA (MOVES) conducted in France, Germany, Poland and Spain evaluating treatment with CS+GH versus celecoxib in 606 patients with Kellgren and Lawrence grades 2-3 knee osteoarthritis and moderate-to-severe pain (Western Ontario and McMaster osteoarthritis index (WOMAC) score ?301; 0-500 scale). Patients were randomised to receive 400 mg CS plus 500 mg GH three times a day or 200 mg celecoxib every day for 6 months. The primary outcome was the mean decrease in WOMAC pain from baseline to 6 months. Secondary outcomes included WOMAC function and stiffness, visual analogue scale for pain, presence of joint swelling/effusion, rescue medication consumption, Outcome Measures in Rheumatology Clinical Trials and Osteoarthritis Research Society International (OMERACT-OARSI) criteria and EuroQoL-5D.ResultsThe adjusted mean change (95% CI) in WOMAC pain was -185.7 (-200.3 to -171.1) (50.1% decrease) with CS+GH and -186.8 (-201.7 to -171.9) (50.2% decrease) with celecoxib, meeting the non-inferiority margin of -40: -1.11 (-22.0 to 19.8; p=0.92). All sensitivity analyses were consistent with that result. At 6 months, 79.7% of patients in the combination group and 79.2% in the celecoxib group fulfilled OMERACT-OARSI criteria. Both groups elicited a reduction >50% in the presence of joint swelling; a similar reduction was seen for effusion. No differences were observed for the other secondary outcomes. Adverse events were low and similarly distributed between groups.ConclusionsCS+GH has comparable efficacy to celecoxib in reducing pain, stiffness, functional limitation and joint swelling/effusion after 6 months in patients with painful knee osteoarthritis, with a good safety profile.Trial registration numberNCT01425853.

Project description:IntroductionChondroitin 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.MethodsChondrocytes obtained from three healthy donors were treated with GS 10 mM and/or CS 200 μg/mL, and then stimulated with interleukin-1β (IL-1β) 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.ResultsA 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-1β in chondrocytes.ConclusionsCS 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 IL1β-stimulated human articular chondrocytes.

Project description:Cationic liposomes composed of a novel lipid (N-{6-amino-1-[N-(9Z) -octadec9-enylamino] -1-oxohexan-(2S) -2-yl} -N'- {2- [N, N-bis(2-aminoethyl) amino] ethyl} -2-hexadecylpropandiamide) (OO4) and dioleoylphosphatidylethanolamine (DOPE) possess high amounts of amino groups and are promising systems for lipofection. Moreover, these cationic liposomes can also be used as a polycationic entity in multilayer formation using layer-by-layer technique (LbL), which is a method to fabricate surface coatings by alternating adsorption of polyanions and polycations. Since liposomes are suitable for endocytosis by or fusion with cells, controlled release of their cargo on site is possible. Here, a polyelectrolyte multilayer (PEM) system was designed of chondroitin sulfate (CS) and collagen type I (Col I) by LbL technique with OO4/DOPE liposomes embedded in the terminal layers to create an osteogenic microenvironment. Both, the composition of PEM and cargo of the liposomes were used to promote osteogenic differentiation of C2C12 myoblasts as in vitro model. The internalization of cargo-loaded liposomes from the PEM into C2C12 cells was studied using lipophilic (Rhodamine-DOPE conjugate) and hydrophilic (Texas Red-labeled dextran) model compounds. Besides, the use of Col I and CS should mimic the extracellular matrix of bone for future applications such as bone replacement therapies. Physicochemical studies of PEM were done to characterize the layer growth, thickness, and topography. The adhesion of myoblast cells was also evaluated whereby the benefit of a cover layer of CS and finally Col I above the liposome layer was demonstrated. As proof of concept, OO4/DOPE liposomes were loaded with dexamethasone, a compound that can induce osteogenic differentiation. A successful induction of osteogenic differentiation of C2C12 cells with the novel designed liposome-loaded PEM system was shown. These findings indicate that designed OH4/DOPE loaded PEMs have a high potential to be used as drug delivery or transfection system for implant coating in the field of bone regeneration and other applications.

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Biomarkers, type II collagen, glucosamine and chondroitin sulfate in osteoarthritis follow-up: the "Magenta osteoarthritis study".

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