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Background: In a previous study, the 84-day administration of glycosaminoglycans (GAGs), with or without native collagen type II (NC), in an osteoarthritis (OA)-induced rabbit model slowed down OA progression, improved several micro- and macroscopic parameters and magnetic resonance imaging (MRI) biomarkers in cartilage, and increased hyaluronic acid levels in synovial fluid. To elucidate the potential underlying mechanisms, a transcriptomics approach was conducted using medial femoral condyle and trochlea samples. Results: The administration of chondroitin sulfate (CS), glucosamine hydrochloride (GlHCl), and hyaluronic acid (HA), with (CGH-NC) or without (CGH) NC, strongly modulated several genes involved in chondrocyte extracellular matrix (ECM) remodeling and homeostasis when compared to non-treated rabbits (CTR group). Notably, both treatments shared the main mechanism of action, which was related to ECM modulation through the down-regulation of genes encoding proteolytic enzymes, such as ADAM metallopeptidase with thrombospondin type 1 motif, 9 (Adamts9), and the overexpression of genes with a relevant role in the synthesis of ECM components, such as aggrecan (Acan) in both CGH-NC and CGH groups, and fibronectin 1 (Fn1) and collagen type II, alpha 1 (Col2A1) in the CGH group. Furthermore, there was a significant modulation at the gene expression level of the mTOR signaling pathway, which is associated with the regulation of the synthesis of ECM proteolytic enzymes, only in CGH-NC-supplemented rabbits. This modulation could account for the better outcomes concerning the microscopic and macroscopic evaluations reported in these animals. Conclusions: In conclusion, the expression of key genes involved in chondrocyte ECM remodeling and homeostasis was significantly modulated in rabbits in response to both CGH and CGH-NC treatments, which would partly explain the mechanisms by which these therapies exert beneficial effects against OA. [ABSTRACT FROM AUTHOR]

The review considers the full spectrum of currently known autoantigens in osteoarthritis (OA) and discusses their role in the development and/or persistence of synovitis and the initiation of subsequent destruction of articular cartilage with the development of an autoimmune response and auto-inflammation. Of great interest are methods of drug prevention of OA considering autoimmunity responses and associated auto-inflammation, including the use of pharmaconutraceuticals.Preclinical and clinical studies of the safety and efficacy of pharmaconutraceuticals containing native type II collagen are presented. A clear relationship between the composition/chemical structure of the collagen components and its mechanism of action and efficacy is discussed. Taking into account the autoimmune pathogenesis of OA, new combined pharmaconutraceuticals aimed at reducing the manifestations of autoinflammation (chondroitin sulfate, glucosamine sulfate) are developed. They have an optimal ratio of active ingredients with a sufficient level of evidence, which allows enhancing their beneficial pharmacological effects.

Purpose: Knee osteoarthritis (OA) is the most common form of clinical arthritis in middle-aged and older individuals. Undenatured or native type II (TII) collagen derived from the chicken sternum has a good therapeutic effect on relieving severe pain of OA. Hence, the present study aimed to investigate the efficacy and safety of TII collagen (Native CT-II®) in individuals with knee OA. Methods: We conducted a 12-week randomised, double-blind, placebo-controlled, parallel-group study on 101 participants aged 40–65 years with knee OA. The participants were randomised to receive either TII collagen, glucosamine hydrochloride + chondroitin sulfate (G + C) or a placebo. The primary outcome was an improvement in the joint health of the participants assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) compared to G + C and placebo. Results: Compared with the placebo group (n = 27), the TII collagen group (n = 29) and G + C group (n = 29) significantly improved the overall joint health measured by the change in WOMAC total score (week 12: TII collagen = -32.47 ± 19.51 and G + C = -33.74 ± 24.64 vs. placebo = -13.84 ± 17.61; p < 0.05) and relieved knee joint pain (week 12: TII collagen = -5.69 ± 3.66 and G + C = -6.03 ± 4.72 vs. placebo = -2.71 ± 3.95; p < 0.05). The statistically significant effect was observed as early as 4 weeks after the investigational product administration. Additionally, the TII collagen was more effective in improving the quality of life than the G + C. Conclusion: TII collagen not only has a significantly better effect and high safety profile for OA but also improves the quality of life of patients. Level of Evidence: Level 1 – Randomized Controlled Trial. Trial registration: ClinicalTrials.gov Identifier: NCT04470336; First submitted date: July 08, 2020; First posted date: July 14, 2020. [ABSTRACT FROM AUTHOR]

Simple Summary: Osteoarthritis is an incurable chronic disease. For this reason, new therapies are constantly emerging to improve clinical signs and the quality of life of our pets. Chondroitin sulfate, glucosamine and hyaluronic acid have been proven effective and are the most widely used in many formulations. In the present study, adding native type II collagen to the combination of chondroitin sulfate, glucosamine and hyaluronic acid showed improvements on osteoarthritis progression in an experimental model of osteoarthritis induced by transection of the cranial cruciate ligament of the knee in New Zealand white rabbits. Disease progression was monitored at different time points using magnetic resonance imaging biomarkers, measurement of hyaluronic acid in synovial fluid, and macroscopic and microscopic evaluations of cartilage, synovial membrane and subchondral bone. Overall, our results showed that adding native type II collagen to a combination of glycosaminoglycans allows a significantly slower osteoarthritis progression, compared to glycosaminoglycans alone. A prospective, experimental, randomized, double blinded study was designed to evaluate the effects of glycosaminoglycans, with or without native type II collagen (NC), in an osteoarthritis model induced by cranial cruciate ligament transection. The following compounds were tested: chondroitin sulfate (CS), glucosamine hydrochloride (GlHCl), hyaluronic acid (HA) and NC. Fifty-four female 12-week-old New Zealand rabbits were classified into three groups: CTR (control–no treatment), CGH (CS + GlHCl + HA) and CGH-NC (CS + GlHCl + HA + NC). Each group was subdivided into three subgroups according to survival times of 24, 56 and 84 days. Over time, all rabbits developed degenerative changes associated with osteoarthritis. CGH-NC showed significantly improved values on macroscopic evaluation, compared to CTR and CGH. Microscopically, significantly better results were seen with CGH and CGH-NC, compared to CTR, and synovial membrane values were significantly better with CGH-NC compared to CGH. A significant improvement in magnetic resonance imaging biomarkers was also observed with CGH-NC in cartilage transversal relaxation time (T2) and subchondral bone D2D fractal dimension in the lateral condyle. In conclusion, our results show beneficial effects on joint health of CGH and CGH-NC and also supports that adding NC to CGH results in even greater efficacy. [ABSTRACT FROM AUTHOR]

Abstract Purpose Knee osteoarthritis (OA) is the most common form of clinical arthritis in middle‐aged and older individuals. Undenatured or native type II (TII) collagen derived from the chicken sternum has a good therapeutic effect on relieving severe pain of OA. Hence, the present study aimed to investigate the efficacy and safety of TII collagen (Native CT‐II®) in individuals with knee OA. Methods We conducted a 12‐week randomised, double‐blind, placebo‐controlled, parallel‐group study on 101 participants aged 40–65 years with knee OA. The participants were randomised to receive either TII collagen, glucosamine hydrochloride + chondroitin sulfate (G + C) or a placebo. The primary outcome was an improvement in the joint health of the participants assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) compared to G + C and placebo. Results Compared with the placebo group (n = 27), the TII collagen group (n = 29) and G + C group (n = 29) significantly improved the overall joint health measured by the change in WOMAC total score (week 12: TII collagen = ‐32.47 ± 19.51 and G + C = ‐33.74 ± 24.64 vs. placebo = ‐13.84 ± 17.61; p

A prospective, experimental, randomized, double blinded study was designed to evaluate the effects of glycosaminoglycans, with or without native type II collagen (NC), in an osteoarthritis model induced by cranial cruciate ligament transection. The following compounds were tested: chondroitin sulfate (CS), glucosamine hydrochloride (GlHCl), hyaluronic acid (HA) and NC. Fifty-four female 12-week-old New Zealand rabbits were classified into three groups: CTR (control–no treatment), CGH (CS + GlHCl + HA) and CGH-NC (CS + GlHCl + HA + NC). Each group was subdivided into three subgroups according to survival times of 24, 56 and 84 days. Over time, all rabbits developed degenerative changes associated with osteoarthritis. CGH-NC showed significantly improved values on macroscopic evaluation, compared to CTR and CGH. Microscopically, significantly better results were seen with CGH and CGH-NC, compared to CTR, and synovial membrane values were significantly better with CGH-NC compared to CGH. A significant improvement in magnetic resonance imaging biomarkers was also observed with CGH-NC in cartilage transversal relaxation time (T2) and subchondral bone D2D fractal dimension in the lateral condyle. In conclusion, our results show beneficial effects on joint health of CGH and CGH-NC and also supports that adding NC to CGH results in even greater efficacy.

Background: Early knee osteoarthritis (OA) treatment is multimodal, with physical therapy and pharmacotherapy commonly used. Although popular, oral supplements like glucosamine and diacerein have not been reported to have high efficacy. Undenatured collagen type II (UC-II) has been introduced for therapy in early OA; it helps in cartilage repair and preservation. The present review was done to ascertain its efficacy in pain relief and knee function., Materials and Methods: A systematic literature search was performed on MEDLINE (PubMed), Embase, Scopus, and Cochrane Library for published literature; studies comparing the outcome of UC-II supplementation with placebo/control in adult humans with early knee OA were included. The outcomes evaluated were VAS Score, quality of life - Western Ontario and McMaster Universities (WOMAC-score), Knee function, Knee range of motion, and any complications during the course of treatment., Results: A total of 293 results were obtained after a primary search; 8 randomized control trials (RCT) were finally included. A total of 243 patients received UC-II supplementation (91 men and 152 women). The overall mean age range for the intervention group was 53.5±0.99 to 68.7±5.3 years across all included studies, and the mean follow-up duration was 3 to 6 months. Outcome measures like WOMAC and VAS scores showed better outcomes with UC-II in comparison to placebo. Walking measurements improved significantly from the baseline, reflected in improved timed up-and-go and 6-minute walk tests (6MWT). The overall complications were similar to other supplements., Conclusion: With limited literature, UC-II has shown promise as a potent supplement in early knee OA with good pain relief and improved function. However, further large-scale studies are needed to substantiate these findings., Competing Interests: None., (AJTR Copyright © 2023.)

Objective: The aim of this randomized controlled study was to evaluate the efficacy of oral native type II collagen treatment on the symptoms and biological markers of cartilage degradation, when given concomitantly with acetaminophen in patients with knee osteoarthritis. Materials and Methods: Thirty-nine patients diagnosed with knee osteoarthritis were included and randomly distributed into two groups: one treated with 1500 mg/day of acetaminophen (group AC; n=19) and the other treated with 1500 mg/day of acetaminophen plus 10 mg/day of native type II collagen (group AC+CII; n=20) for 3 months. Visual Analogue Scale (VAS) at rest and during walking, Western Ontario McMaster (WOMAC) pain, WOMAC function, and Short Form-36 (SF-36) scores, were recorded. Coll2-1, Coll2-1NO2 and Fibulin-3 levels were quantified in urine as bio-markers of disease progression.ClinicalTrials.gov: NCT02237989. Results: After 3 months of treatment, significant improvements compared to baseline were reported in joint pain (VAS walking), function (WOMAC) and quality of life (SF-36) in the AC+CII group, while only improvements in some subscales of the SF-36 survey and VAS walking were detected in the AC group. Comparisons between the groups revealed a significant difference in VAS walking score in favour of the AC+CII group as compared to AC group. Biochemical markers of cartilage degradation in urine did not significantly improve in any of the groups. Conclusion: All in all, these results suggest that native type II collagen treatment combined with acetaminophen is superior to only acetaminophen for symptomatic treatment of patients with knee osteoarthritis. [ABSTRACT FROM AUTHOR]