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Disparate efficacy of collagen hydrolysate and glucosamine on the extracellular matrix metabolism of articular chondrocytes
Abstract
Introduction
Glucosamine has been used in the treatment of osteoarthritis (OA) for several years. More recently, collagen fragments were shown to provide a positive effect on joint health. The objective of this study was to investigate the efficacy of a specific type of collagen hydrolysate (CH) on the biosynthesis of ECM macromolecules in comparison with glucosamine sulfate (GS) and glucosamine hydrochloride (GH) in a chondrocyte culture model.
Materials & Methods
Primary porcine articular and human femoral chondrocytes were cultured under reduced oxygen conditions. The culture medium was supplemented with various concentrations of CH. In parallel experiments chondrocytes were treated with either GS or GH. At the end of the culture period the amount of cell-associated proteoglycans (PGs) and the extent of PG synthesis were quantified by measuring 35S-sulfate incorporation. In addition, type II collagen biosynthesis was quantified by 14C-proline incorporation. The amount of aggrecan and type II collagen accumulated in the extracellular matrix (ECM) were determined by Western Blotting.
Results
Supplementation of the culture medium with CH resulted in a statistically significant (p<0.05) increase of PG synthesis. The amount of cell-associated PGs was almost doubled after CH treatment, compared with the control cells. Administration of CH was also associated with increased aggrecan expression and a statistically significant (p<0.05) 1.5-fold increase of type II collagen biosynthesis. In contrast, the administration of GS or GH had no stimulatory effect on the type II collagen biosynthesis of the chondrocytes. Moreover, supplementation of glucosamine had no significant effect on the amount of cell-associated PGs compared to the controls.
Conclusion
These results indicate a stimulatory effect of CH on the synthesis of PG and type II collagen. In contrast, GS and GH failed to stimulate the synthesis of ECM macromolecules by chondrocytes.
These data suggest that CH may help reduce degenerative changes of the ECM by stimulating anabolic processes in cartilage tissue.
... Steffen Oesser and colleagues were the first group to report about the absorption, accumulation and action of CH. Bovine CH (3.1-3.3 kDa, FORTIGAL, Gelita AG) can stimulate collagen and proteoglycan synthesis in chondrocytes [11][12][13]. Kenneth and colleagues discovered that 3 kDa of bovine CH (Gelita) elevated sulfated glycosaminoglycan (sGAG) and collagen contents in chondrocyte-seeded agarose hydrogels [14]. On the other hand, fish collagen peptide (3 kDa) showed the chondroprotective effect in combination with glucosamine in a rat ACLT model [15]. ...
... c Bar graphs of band densities showed mean ± SEM. The statistic was analyzed by ANOVA with multiple comparisons LSD that p < 0.05, * when compared to control group, # when compared to IL-1β group (3-3.7 kDa) could also increase sGAG and collagen content in normal condition of bovine chondrocyte monolayers under reduced O 2 condition [11][12][13]. On the contrary, Fichter and colleagues reported that type II collagen fragments from bovine cartilage, which was less than 10 kDa, could induce MMP3 and MMP13 expression together with MMP2 and MMP9 activity in chondrocyte cultivation [3]. ...
Osteoarthritis is a degenerative joint disease in which interleukin-1β plays a major role in the inflammatory process. Administration of collagen hydrolysate was an optional treatment of osteoarthritis. Fish has become an interesting source of collagen hydrolysate because of religious reason and there is no risk from mad cow disease. However, the effects of different sizes of fish collagen hydrolysate on cartilage and chondrocyte metabolism have not been well studied yet. This study examined the effect of different sizes of fish collagen hydrolysate on cartilage metabolism. Three different sizes of fish collagen hydrolysate were prepared by size exclusion using centrifugation, which composed of small fraction (<3 kDa), medium fraction (3-10 kDa) and large fraction (>10 kDa). Using porcine cartilage explant, in physiological condition, all the three fractions had no effect on cartilage metabolism, but they could induce pro-MMP3 and pro-MMP13 secretions through activation of p-ERK and p-p38. In pathological condition induced by interleukin-1β and oncostatin-M, small and medium fractions showed additive effect with interleukin-1β and oncostatin-M on cartilage degradation, whereas large size had no effect. In addition, the effect of small size occurred through further activation of p-p65, which resulted in further induction of active-MMP13, while medium size had a different mechanism. In conclusion, all three fractions fish collagen hydrolysate had no effect on cartilage metabolism in physiological condition, but small and medium fractions had adverse effect on cartilage in pathological condition. Taken together, various sizes of fish collagen hydrolysate showed different effects on cartilage metabolism. Therefore, different sizes of fish collagen hydrolysates play different roles on cartilage metabolism, especially in the pathological condition.
... Evidence further suggests that collagen exerts a stimulatory effect on type II collagen biosynthesis in chondrocytes, indicating a potential feedback mechanism that helps regulate collagen turnover within cartilage tissue [24]. Moreover, collagen has demonstrated the ability to enhance the synthesis of both proteoglycans and type II collagen, supporting anabolic processes that may counteract degenerative changes in the extracellular matrix of cartilage tissue [25]. A later study confirms that collagen peptide supplementation reduces catabolic processes, significantly decreasing inflammatory cytokines and proteases in canine chondrocytes, while improving the biosynthesis of type II collagen, elastin, and aggrecan [14]. ...
As dogs age, the decline in mobility is a common physiological change. The incorporation of complementary feeds can be an effective strategy to support and preserve joint function and mobility, contributing to the maintenance of overall musculoskeletal health and comfort in geriatric dogs. Privately owned dogs aged over six years, exhibiting reduced mobility and no changes in their mobility management within the last three months, were recruited for this study. They were administered a chicken cartilage hydrolysate complementary feed containing a complex of glycosaminoglycans and type II collagen (Glycosane®, MP Labo, France) once daily for 56 days. Assessments were conducted at baseline (D0) and follow-up visits at D7, D28, and D56. Mobility, pain intensity, and pain interference were evaluated using a revised Liverpool Osteoarthritis in Dogs (LOAD) scale and a Canine Brief Pain Inventory (CBPI). Owners also completed a questionnaire assessing quality of life (QoL), with seven questions on the animal’s well-being (QoL1) and seven questions on the owner’s well-being (QoL2). A total of 21 dogs were included in the study, with 71% of owners reporting enhanced mobility by D56. Notable improvements were observed in half of the cases after 21 days of supplementation, with 39% of cases showing significant changes as early as 14 days. Revised LOAD scores demonstrated a significant improvement over time (p=0.0019). CBPI severity scores decreased significantly from baseline to D28 and D56 (p=0.0300 and p=0.0271, respectively). The CBPI QoL score also significantly improved at D56 compared to D7 (p=0.0440). The overall QoL score showed a significant improvement by D56 compared to baseline (p=0.0089), with a particular improvement in QoL1 (p=0.0015). The supplement was rated highly for ease of use (mean score 4.4/5), with an excellent compliance (95%). This complementary feed demonstrates significant benefits in enhancing mobility and quality of life in senior dogs. Its high ease of administration supports owner compliance and satisfaction. These findings suggest that Glycosane® is a valuable nutritional aid in maintaining canine mobility. Further studies with larger cohorts and a controlled group are recommended to confirm these results.
... The observed increase in tendon thickness may indicate a positive structural adaptation, potentially enhancing the tendon's capacity to withstand the substantial mechanical loads experienced during skating. This finding aligns with previous research by Schunck et al. [43], who reported improved collagen synthesis in the extracellular matrix of tendons following CH supplementation. Moreover, it extends our understanding of tendon adaptations to nutritional interventions, suggesting that such changes can occur within a relatively short timeframe (three months in our case) in young elite athletes. ...
The use of dietary supplements is widespread in sports and fitness, with many products containing multiple ingredients. Among supplements often consumed to support musculotendinous health, collagen hydrolysate (CH) has gained popularity for its potential in improving joint comfort and function. This single-blind quasi-experimental study investigated the effects of a three-month oral supplementation with a specific CH-based product, Chondrovita FIT® (Bone Srl, Rome, Italy), on tendon structure in elite Italian skaters. Eighteen male and female elite skaters (mean age: 21 ± 3 years) participated, receiving daily pre-workout (4500 mg CH) and post-workout (2500 mg CH) doses. Tendon structure in the patellar and peroneal tendons was assessed using ultrasound imaging at baseline and post-supplementation. Results showed a significant increase in tendon thickness in both the patellar and peroneal tendons after supplementation, although no changes were observed in the tendon cross-sectional area. These findings suggest that Chondrovita FIT® supplementation may induce beneficial structural changes in tendons, potentially supporting tendon health and performance in high-load sports. However, further research is needed to confirm long-term effects and functional outcomes.
... Glucosamine has been extensively studied [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] showing positive results in the clinical management of pain and structural improvements [19]. Chondroitin sulfate coupled to Glucosamine, or by itself, has been the center of significant studies [20], but many other compounds synthetic or natural have been investigated, including Vitamin C [21][22][23][24][25]. Particular interest has been paid to Collagen Hydrolysates (CHs) and Fucoidans [26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44]. CH is obtained by the enzymatic hydrolysis of collage nous tissues from mammals. ...
... Currently, glucosamine and chondroitin are the two most commonly used nutraceuticals that provide medicinal, therapeutic, and health benefits to arthritic patients 6,7 . For example, treatment with collagen derivatives has been proposed to provide an adequate supply of nutrients required for cartilage repair and maintenance 8,9 , improve and preserve the quality of the subchondral bone 10,11 , and maintain the overall health of articular cartilage and subchondral bone 12,13 . Over the past several years, a novel nutraceutical undenatured type II collagen (UC-II) from chicken sternum cartilage has been studied in knee OA subjects 14e16 . ...
Objective:
The aim of this study was to determine the ability of undenatured native chicken type II collagen (UC-II) to prevent excessive articular cartilage deterioration in a rat model of osteoarthritis (OA).
Methods:
Twenty male rats were subjected to partial medial meniscectomy tear (PMMT) surgery to induce OA. Immediately after the surgery ten rats received vehicle and another ten rats oral daily dose of UC-II at 0.66 mg/kg for a period of 8 weeks. In addition ten naïve rats were used as an intact control and another 10 rats received sham surgery. Study endpoints included a weight-bearing capacity of front and hind legs, serum biomarkers of bone and cartilage metabolism, analyses of subchondral and cancellous bone at the tibial epiphysis and metaphysis, and cartilage pathology at the medial tibial plateau using histological methods.
Results:
PMMT surgery produced moderate OA at the medial tibial plateau. Specifically, the deterioration of articular cartilage negatively impacted the weight bearing capacity of the operated limb. Immediate treatment with the UC-II preserved the weight-bearing capacity of the injured leg, preserved integrity of the cancellous bone at tibial metaphysis and limited the excessive osteophyte formation and deterioration of articular cartilage.
Conclusion:
Study results demonstrate that a clinically relevant daily dose of UC-II when applied immediately after injury can improve the mechanical function of the injured knee and prevent excessive deterioration of articular cartilage.
... In vitro studies have shown that the addition of collagen hydrolysate in the culture medium of chondrocytes increased the secretion of type II collagen in a dose-dependent fashion, suggesting a likely feedback mechanism to regulate the collagen turnover in cartilage tissue [9]. Chondrocytes also responded to collagen hydrolysate addition with a significant increase in proteoglycan synthesis, aggrecan expression and 1.5 fold increment in type II collagen biosynthesis [10]. ...
... Glucosamine has been extensively studied [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] showing positive results in the clinical management of pain and structural improvements [19]. Chondroitin sulfate coupled to Glucosamine, or by itself, has been the center of significant studies [20], but many other compounds synthetic or natural have been investigated, including Vitamin C [21][22][23][24][25]. Particular interest has been paid to Collagen hydrolysates (CHs) and Fucoidans [26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44]. CH is obtained by the enzymatic hydrolysis of collagenous tissues from mammals. ...
... The main characteristic of hydrolyzed collagen is its amino acid composition, which is identical to collagen, thus providing high levels of glycine and proline, two amino acids essential for the stability and regeneration of cartilage [16,17]. Proteoglycans synthesis, aggrecan gene expression and type II collagen synthesis are increased with hydrolyzed collagen in bovine and porcine articular chondrocytes [18,19]. Epigallocatechin-3-gallate (EGCG) is a major component of the polyphenolic fraction of green tea and exhibits anti-oxidant, anti-tumor and antimutagenic activities [7,20]. ...
The main objective of this study was to assess the in vitro effects of curcuminoids extract, hydrolyzed collagen and green tea extract in normal bovine chondrocytes and osteoarthritic human chondrocytes cultured in monolayer. This study also investigated the synergic or additive effects of these compounds. Enzymatically isolated primary bovine or human chondrocytes were cultured in monolayer until confluence and then incubated for 24 hours or 48 hours in the absence or in the presence of interleukin-1beta and with or without curcuminoids extract, hydrolyzed collagen or green tea extract, added alone or in combination, at different concentrations. Cell viability was neither affected by these compounds, nor by interleukin 1beta. In the absence of interleukin-1beta, compounds did not significantly affect bovine chondrocytes metabolism. In human chondrocytes and in the absence of interleukin 1beta, curcuminoids extract alone or in combination with hydrolyzed collagen and green tea extract significantly inhibited matrix metalloproteinase-3 production. In interleukin-1beta-stimulated bovine chondrocytes, interleukin-6, inducible nitric oxide synthase, cyclooxygenase2, matrix metalloproteinase 3, a disintegrin and metalloproteinase with thrombospondin type I motifs 4 and a disintegrin and metalloproteinase with thrombospondin type I motifs 5 expressions were decreased by curcuminoids extract alone or in combination with hydrolyzed collagen and green tea extract. The combination of the three compounds was significantly more efficient to inhibit interleukin-1beta stimulated matrix metalloproteinase-3 expression than curcuminoids extract alone. In interleukin-1beta-stimulated human chondrocytes, nitric oxide, interleukin-6 and matrix metalloproteinase 3 productions were significantly reduced by curcuminoids extract alone or in combination with hydrolyzed collagen and green tea extract. These findings indicate that a mixture of curcuminoids extract, hydrolyzed collagen and green tea extract has beneficial effects on chondrocytes culture in inflammatory conditions and provide a preclinical basis for the in vivo testing of this mixture.
... The three major groups of collagen derivatives clinically used for arthritis treatment are based on the various degrees of hydrolysis of collagen: gelatin, collagen hydrolysate and native undenatured collagen [5]. Analogous working mechanisms has been described for gelatin and collagen hydrolysate: after oral administration peptides can be used as building blocks for the cartilage [6][7][8]. Moreover, it is hypothesized that collagen hydrolysate also influences bone metabolism [9,10] or the vascular system involved in the atheromatous disease of the subchondral bone [11,12]. ...
Osteoarthritis is the most widespread joint-affecting disease. Patients with osteoarthritis experience pain and impaired mobility resulting in marked reduction of quality of life. A progressive cartilage loss is responsible of an evolving disease difficult to treat. The characteristic of chronicity determines the need of new active disease modifying drugs. Aim of the present research is to evaluate the role of low doses of native type II collagen in the rat model of osteoarthritis induced by sodium monoiodoacetate (MIA).
1, 3 and 10 mg kg-1 porcine native type II collagen were daily per os administered for 14 days starting from the day of MIA intra-articular injection.
On day 14, collagen-treated rats showed a significant prevention of pain threshold alterations induced by MIA. Evaluation were performed on paws using mechanical noxious (Paw pressure test) or non-noxious (Electronic Von Frey test) stimuli, and a decrease of articular pain was directly measured on the damaged joint (PAM test). The efficacy of collagen in reducing pain was as higher as the dose was lowered. Moreover, a reduced postural unbalance, measured as hind limb weight bearing alterations (Incapacitance test), and a general improvement of motor activity (Animex test) were observed. Finally, the decrease of plasma and urine levels of CTX-II (Cross Linked C-Telopeptide of Type II Collagen), a biomarker of cartilage degradation, suggests a collagen-dependent decrease of structural joint damage.
These results describe the preclinical efficacy of low dosages of native type II collagen as pain reliever by a mechanism that involves a protective effect on cartilage.
... Three possible mechanisms of CH (and gelatine) can be proposed. Firstly, studies using oral administration of radioactive-labelled gelatine in mice and in vitro studies with CH, suggest that peptides can be used as building blocks for the cartilage 5,8,9 . However, the data of these short-term experiments of chondrocytes in monolayer were not confirmed in longer-term studies with chondrocytes in 3D constructs 10,11 . ...
Objective:
Osteoarthritis (OA) is one of the most prevalent musculoskeletal diseases. Collagen derivatives are candidates for disease-modifying OA drugs. This group of derivatives can be divided into undenatured collagen (UC), gelatine and collagen hydrolysate (CH). Collagen derivatives are marketed as having direct chondroprotective action and reducing complaints of OA. This review summarizes the evidence for the effectiveness of symptomatic and chondroprotective treatment with collagen derivatives in patients with OA.
Methods:
Eligible randomised controlled trials (RCTs) and quasi-RCTs were identified by searching PubMed, Embase and the Cochrane Central Register of Controlled Trials until November 2011. Methodological quality was assessed using methods of the Cochrane Back Review Group.
Results:
Eight studies were identified: six on CH, two on gelatine, and one on UC. The pooled mean difference based on three studies for pain reduction measured with the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index comparing CH with placebo was -0.49 (95% CI -1.10-0.12). However, some studies report significant between-group differences in pain when measured with a visual analogical scale (VAS) or other instruments, or when CH is compared with glucosamine sulphate. For disability no significant between-group mean differences were found when comparing CH with placebo. Gelatine compared with placebo and with alternative therapies was superior for the outcome pain. UC compared with glucosamine+chondroitin showed no significant between-group differences for pain and disability. The most reported adverse events of collagen derivatives were mild to moderate gastro-intestinal complaints. The overall quality of evidence was moderate to very low.
Conclusions:
There is insufficient evidence to recommend the generalized use of CHs in daily practice for the treatment of patients with OA. More independent high-quality studies are needed to confirm the therapeutic effects of collagen derivatives on OA complaints.
... This study demonstrated the stimulatory potency of CH on type II collagen and PG synthesis, as well as aggrecan expression by chondrocytes. This result was also reported in a scientific communication on CH effect in porcine chondrocytes 50 . In addition, an in vivo study with STR/ort mice which spontaneously developed OA 51 has shown that long-term CH supplementation may decrease OA cartilage degeneration and delay the progression of OA. ...
The aim of this first global systematic review on selected nutraceuticals was to synthesize and evaluate scientific relevant data available in the literature. Evidences that can support health, physiological or functional benefit on osteoarthritis (OA) were gathered and the level of evidence relative to each of these ingredients was highlighted.
Relevant scientific data (positive or not) regarding OA were searched for five groups of compounds (avocado/soybean unsaponifiables (ASU), n-3 polyunsaturated fatty acids, collagen hydrosylates (CHs), vitamin D, polyphenols) within preclinical (in vitro and in vivo), epidemiological, and clinical studies. The following criteria were evaluated to assess the methodology quality of each study: (1) study question; (2) study population; (3) primary endpoint; (4) study design (randomization, control, blinding, duration of follow up); (5) data analysis and interpretation. A scientific consensus was determined for all studied nutraceuticals to evaluate their efficacy in OA.
The studied compounds demonstrated different potencies in preclinical studies. Most of them have demonstrated anti-catabolic and anti-inflammatory effects by various inhibitory activities on different mediators. Vitamin D showed a pro-catabolic effect in vitro and the polyphenol, Genistein, had only anti-inflammatory potency. The evaluation of the clinical data showed that ASU was the only one of the studied ingredients to present a good evidence of efficacy, but the efficient formulation was considered as a drug in some countries. Pycnogenol showed moderate evidence of efficacy, and vitamin D and collagen hydrolysate demonstrated a suggestive evidence of efficacy, whereas curcumin, epigallocatechin-3-gallate (EGCG) and resveratrol had only preclinical evidence of efficacy due to the lack of clinical data. The literature gathered for n-3 PUFA, nobiletin and genistein was insufficient to conclude for their efficacy in OA.
Additional data are needed for most of the studied nutraceuticals. Studies of good quality are needed to draw solid conclusions regarding their efficacy but nutraceuticals could represent good alternates for OA management. Their use should be driven by any recommendations.
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