Collagen Metabolism of Human Osteoarthritic Articular Cartilage as Modulated by Bovine Collagen Hydrolysates

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.

Improvement of activity-related knee joint discomfort following supplementation of specific collagen peptides

“…The specific effects seems to be dependent on the collagen hydrolysate concentration, the experimental conditions (Ng et al 2007), and specific the characteristic of the tested collagen hydrolysates (Schadow et al 2013).…”

“…Other in vitro experiments showed an increase of protease activity after collagen fragments supplementation (Fichter et al 2006;Jennings et al 2001). There is evidence that the effects of collagen hydrolysate depend on the concentration, the experimental conditions, (Ng et al 2007), and the characteristic of the tested collagen hydrolysates (Schadow et al 2013). However, the clinical relevance of the observed effects needs to be clarified.…”

Supplements und Injektionen bei Arthrose und Knorpelschäden

“…In den vergangenen Jahren hat das Kollagen-Hydrolysat Eingang in die nutritive Therapie gefunden, nachdem in Tierstudien mit radioaktiv markiertem KollagenHydrolysat gezeigt werden konnte, dass eine Aufnahme sowohl der Peptide als auch des Makromoleküls in den Gelenkknorpel belegbar ist [33]. In-vitro-Studien belegen darüber hinaus eine erhöhte Kollagensyntheserate in OA-Gelenkexplants durch die Zugabe von KollagenHydrolysat in das Kulturmedium [40]. Eine geringe Zahl klinischer Studien mit eingeschränkter Evidenz konnten bisher nur uneinheitlich positive Effekte bei der Schmerzreduktion und bei der Funktionsverbesserung der OA-Gelenke nachweisen [39].…”

Collagen supplementation as a complementary therapy for the prevention and treatment of osteoporosis and osteoarthritis: a systematic review

“…Despite the great expectations for the positive results of studies such as Bello & Oesser, 36 Schadow et al, 41 concluded in their clinical trials with radioactive proline in vitro models that even at high doses (10mg/ml), collagen does not exert a stimulatory effect on collagen biosynthesis by human cartilage, regardless of the degree of change in OA. Different results can occur between studies because of differences in applied analytical methods, species, and the age and health of the joints.…”

“…Furthermore, the determination of the radioactive proline incorporation rate without specific separation of total proteins does not reflect the true collagen synthesis rate, since the proline enrichment in the collagen compared to other proteins is not described. However Schadow et al 41 stated that collagen hydrolysate preparations could contain therapeutically active peptides, but extensive studies are needed, as well as clinical trials, before these are applied as nutraceuticals.…”