Abstract
Destruction of articular cartilage is a characteristic feature of osteoarthritis (OA). Collagen hydrolysates are mixtures of collagen peptides and have gained huge public attention as nutriceuticals used for prophylaxis of OA. Here, we evaluated for the first time whether different bovine collagen hydrolysate preparations indeed modulate the metabolism of collagen and proteoglycans from human OA cartilage explants and determined the chemical composition of oligopeptides representing collagen fragments. Using biophysical techniques, like MALDI-TOF-MS, AFM, and NMR, the molecular weight distribution and aggregation behavior of collagen hydrolysates from bovine origin (CH-Alpha®, Peptan™ B 5000, Peptan™ B 2000) were determined. To investigate the metabolism of human femoral OA cartilage, explants were obtained during knee replacement surgery. Collagen synthesis of explants as modulated by 0–10 mg/ml collagen hydrolysates was determined using a novel dual radiolabeling procedure. Proteoglycans, NO, PGE2, MMP-1, -3, -13, TIMP-1, collagen type II, and cell viability were determined in explant cultures. Groups of data were analyzed using ANOVA and the Friedman test (n = 5–12). The significance was set to p≤0.05. We found that collagen hydrolysates obtained from different sources varied with respect to the width of molecular weight distribution, average molecular weight, and aggregation behavior. None of the collagen hydrolysates tested stimulated the biosynthesis of collagen. Peptan™ B 5000 elevated NO and PGE2 levels significantly but had no effect on collagen or proteoglycan loss. All collagen hydrolysates tested proved not to be cytotoxic. Together, our data demonstrate for the first time that various collagen hydrolysates differ with respect to their chemical composition of collagen fragments as well as by their pharmacological efficacy on human chondrocytes. Our study underscores the importance that each collagen hydrolysate preparation should first demonstrate its pharmacological potential both in vitro and in vivo before being used for both regenerative medicine and prophylaxis of OA.
Highlights
Collagen hydrolysates are mixtures of collagen peptides and are popular nutriceuticals used for prophylaxis of osteoarthritis (OA)
Biochemical Characterization of Collagen Hydrolysates MALDI-TOF-MS analysis revealed qualitative differences between collagen hydrolysates obtained from different sources with respect to peptides identified in each preparation, width of molecular weight distribution, and the average molecular weight
We show for the first time that (1) the collagen hydrolysates RDH, RDH-N, and CH-alphaH differ with respect to both the molecular weight distribution of collagen fragments and by their biological activities on human chondrocytes
Summary
Collagen hydrolysates are mixtures of collagen peptides and are popular nutriceuticals used for prophylaxis of osteoarthritis (OA). A recently published pilot randomized controlled trial with 30 patients presenting with mild knee OA suggests that delayed gadoliniumenhanced magnetic resonance imaging of cartilage (dGEMERIC) was able to detect a change in the proteoglycan content of cartilage after 24 weeks in patients receiving a collagen hydrolysate formulation [8]. These preliminary data are of limited value due to the small sample size and missing morphometric MRI sequences [8]. The European Food Safety Authority (EFSA) panel on dietetic products, nutrition, and allergies recently concluded that so far, no cause-and-effect relationship between the maintenance of joints and the use of collagen hydrolysates has been shown [9]
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