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Niacinamide and undenatured type II collagen modulates the inflammatory response in rats with monoiodoacetate-induced osteoarthritis.

ABSTRACT: The current work aimed to examine the properties of oral supplementation of niacinamide and undenatured type II collagen (UCII) on the inflammation and joint pain behavior of rats with osteoarthritis (OA). Forty-nine Wistar rats were allocated into seven groups; control (no MIA), MIA as a non-supplemental group with monosodium iodoacetate (MIA)-induced knee osteoarthritis, MIA + undenatured type II collagen (UCII) at 4 mg/kg BW, MIA + Niacinamide at 40 mg/kg BW (NA40), MIA + Niacinamide at 200 mg/kg BW (NA200), MIA + UCII + NA40 and MIA + UCII + NA200. Serum IL-1β, IL-6, TNF-α, COMP, and CRP increased in rats with OA and decreased in UCII and NA groups (p < 0.05). Rats with osteoarthritis had greater serum MDA and knee joint MMP-3, NF-κB, and TGβ protein levels and decreased in treated groups with UCII and NA (p < 0.05). The rats with OA also bore elevated joint diameters with joint pain behavior measured as decreased the stride lengths, the paw areas, and the paw widths, and increased the Kellgren-Lawrence and the Mankin scores (p < 0.05) and decreased in UCII treated groups. These results suggest the combinations with the UCII + NA supplementation as being most effective and reduce the inflammation responses for most OA symptoms in rats.

SUBMITTER: Sahin K

PROVIDER: S-EPMC8289820 | biostudies-literature |

REPOSITORIES: biostudies-literature

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The effect of oral administration of undenatured type II collagen on monosodium iodoacetate-induced osteoarthritis in young and old rats.

Project description:We investigated whether different doses of undenatured type II collagen (undenatured collagen, UC-II) help improve monosodium iodoacetate (MIA)-induced (osteoarthritis) OA in young and old rats. A total of 70 rats were divided into five groups: (1) control; (2) MIA (a single intra-articular injection of MIA); (3)-(5) MIA+ Undenatured Collagen with various oral doses (0.66, 1.33, and 2 mg/kg). The results showed that all doses of undenatured collagen in both age groups reduced knee diameter, while the two higher doses (1.33 mg/kg and 2 mg/kg) reduced the Mankin score and increased most gait measurements as early as day 14 compared to the MIA rats. However, the 2 mg/kg dose showed the best efficacy in improving Mankin score and gait measurements by 28 days post-OA induction. In young but not old rats, all doses of undenatured collagen reduced the Kellgren-Lawrence score compared to the MIA group. Undenatured collagen reduced the levels of most inflammatory and cartilage breakdown markers in serum and knee joint cartilage in both age groups. In conclusion, this data suggests that while all doses of undenatured collagen supplementation may ameliorate MIA-induced OA symptoms, the higher doses showed faster improvement in gait measurements and were more efficacious for overall joint health in rats.

| S-EPMC10119188 | biostudies-literature

Management of Osteoarthritis and Joint Support Using Feed Supplements: A Scoping Review of Undenatured Type II Collagen and <i>Boswellia serrata</i>.

Project description:In the multimodal management of osteoarthritis (OA) in recent decades, the use of feed supplements to maintain joint cartilage has been advocated. The aim of this scoping review is to present the results found in the veterinary literature on the use of undenatured type II collagen and Boswellia serrata in dogs, specifically its use in dogs with clinical signs of OA, healthy dogs after intense exercise or dogs with diseases that predispose the individual to OA. For this purpose, a literature review was carried out using the electronic databases PubMed, Web of Science and Google Scholar, from which a total of 26 records were included in this review: fourteen evaluating undenatured type II collagen, ten evaluating Boswellia serrata and two evaluating the combination of undenatured type II collagen and Boswellia serrata. The review of the records showed that undenatured type II collagen decreases the clinical signs associated with OA, improving the general clinical state with a reduction in the degree of lameness and increase in physical activity or mobility. Evaluating the response to supplementation with Boswellia serrata alone is complicated due to the limited publication of studies and variations in the purity and compositions of the products used, but in general terms, its combination with other feed supplements produces benefits by relieving pain and reducing the clinical signs of OA in dogs. The combination of both in the same product provides results similar to those obtained in undenatured type II collagen studies. In conclusion, undenatured type II collagen and Boswellia serrata are considered a valid option for the multimodal approach to the management of OA and for improving activity during intense exercise, but more studies are needed to conclude whether or not it prevents OA in dogs.

| S-EPMC10000124 | biostudies-literature

Effects of Exercise Combined with Undenatured Type II Collagen on Endurance Capacity, Antioxidant Status, Muscle Lipogenic Genes and E3 Ubiquitin Ligases in Rats.

Project description:The current study aimed to investigate the effect of exercise combined with undenatured type II collagen (UCII) administration on endurance capacity, lipid metabolism, inflammation, and antioxidant status in rats. Twenty-one male Wistar albino rats were divided into three groups as follows: (1) Sedentary control, (2) Exercise (E), (3) Exercise + UCII (4 mg/kg BW/day; E + UCII). The findings showed that the exhaustive running time in the UCII group was significantly prolonged compared to that of the non-supplemented group (p < 0.001). When compared to the control group, total serum cholesterol (TC, p < 0.05) and triglyceride (TG, p < 0.05) levels decreased, while creatinine kinase (CK) levels increased in the E group (p < 0.001). Serum creatinine kinase levels were reduced in the E + UCII group compared to the E group (p < 0.01). Serum lactate, myoglobin (p < 0.01), and osteocalcin levels (p < 0.01) increased significantly in exercised rats compared to sedentary control rats, while serum lactate (p < 0.01) and myoglobin (p < 0.0001) levels decreased in the E + UCII group compared to control. Additionally, UCII supplementation caused significant increases in antioxidant enzyme activities [SOD (p < 0.01) and GSH-Px (p < 0.05)] and decreases in malondialdehyde (MDA) and tumor necrosis factor (TNF-α) levels (p < 0.001). Muscle lipogenic protein (SREBP-1c, ACLY, LXR, and FAS) levels were lower in the E + UCII group than in other groups. In addition, UCII supplementation decreased muscle MAFbx, MuRF-1, myostatin and increased MyoD levels in exercised rats. Moreover, the E + UCII group had lower muscle inflammatory markers [TNF-α (p < 0.0001) and IL-1β (p < 0.01)] than the control group. These results suggest exercise combined with UCII (4 mg/kg BW/day) modulates lipid, muscle, and antioxidant status in rats.

| S-EPMC8002679 | biostudies-literature

UC-II Undenatured Type II Collagen for Knee Joint Flexibility: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Clinical Study.

Project description:Objective: Joint-related stress models have been used in the past to induce a standardized load on physical structures, allowing researchers to observe changes in perceived stress on joints as accurately as possible in healthy individuals. Previous studies support the efficacy of UC-II® undenatured type II collagen ("undenatured collagen") supplementation in maintaining joint health. The purpose of this study was to assess the effect of undenatured collagen on knee flexibility in healthy subjects who experience activity-related joint discomfort (ArJD). Methods: This randomized, double-blind, placebo (PLA)-controlled study was conducted in healthy subjects with ArJD who had no history of osteoarthritis, or joint diseases. Ninety-six (n = 96, 20-55 years old) subjects who reported joint discomfort while performing a standardized single-leg-step-down test were randomized to receive either PLA (n = 48) or 40 mg of undenatured collagen (n = 48) supplementation daily for 24 weeks. Range of motion (ROM) flexion and extension were measured using a digital goniometer. Results: At the end of the study, a statistically significant increase in knee ROM flexion was observed in the undenatured collagen group versus the PLA group (3.23° vs. 0.21°; p = 0.025). In addition, an increase in knee ROM extension by 2.21° was observed over time in the undenatured collagen group (p = 0.0061), while the PLA group showed a nonsignificant increase by 1.27° (p > 0.05). Subgroup analysis by age showed a significant increase in knee ROM flexion in subjects >35 years old in the undenatured collagen supplemented group compared with PLA (6.79° vs. 0.30°; p = 0.0092). Conclusion: Overall, these results suggest that daily supplementation of 40 mg of undenatured collagen improved knee joint ROM flexibility and extensibility in healthy subjects with ArJD.

| S-EPMC9232232 | biostudies-literature

Efficacy and tolerability of an undenatured type II collagen supplement in modulating knee osteoarthritis symptoms: a multicenter randomized, double-blind, placebo-controlled study.

Project description:Undenatured type II collagen (UC-II) is a nutritional supplement derived from chicken sternum cartilage. The purpose of this study was to evaluate the efficacy and tolerability of UC-II for knee osteoarthritis (OA) pain and associated symptoms compared to placebo and to glucosamine hydrochloride plus chondroitin sulfate (GC).One hundred ninety one volunteers were randomized into three groups receiving a daily dose of UC-II (40 mg), GC (1500 mg G & 1200 mg C), or placebo for a 180-day period. The primary endpoint was the change in total Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) from baseline through day 180 for the UC-II group versus placebo and GC. Secondary endpoints included the Lequesne Functional Index (LFI), the Visual Analog Scale (VAS) for pain and the WOMAC subscales. Modified intent-to-treat analysis were performed for all endpoints using analysis of covariance and mixed model repeated measures, while incremental area under the curve was calculated by the intent-to-treat method.At day 180, the UC-II group demonstrated a significant reduction in overall WOMAC score compared to placebo (p = 0.002) and GC (p = 0.04). Supplementation with UC-II also resulted in significant changes for all three WOMAC subscales: pain (p = 0.0003 vs. placebo; p = 0.016 vs. GC); stiffness (p = 0.004 vs. placebo; p = 0.044 vs. GC); physical function (p = 0.007 vs. placebo). Safety outcomes did not differ among the groups.UC-II improved knee joint symptoms in knee OA subjects and was well-tolerated. Additional studies that elucidate the mechanism for this supplement's actions are warranted.CTRI/2013/05/003663 ; CTRI/2013/02/003348 .

| S-EPMC4731911 | biostudies-other

Crocin exerts anti-inflammatory and anti-arthritic effects on type II collagen-induced arthritis in rats.

Project description:CONTEXT:Rheumatoid arthritis (RA) is a common systemic auto-immune disease, which is characterized by chronic and symmetry synovial inflammation. Crocin has been reported to exhibit anti-inflammatory effects in animal models. OBJECTIVE:This study investigates the anti-inflammatory and anti-arthritic effects of crocin on type II collagen-induced arthritis (CIA) in Wistar rats. MATERIALS AND METHODS:The CIA rat model was established and randomly divided into five groups with or without crocin treatment (10, 20 or 40?mg/kg), which was started on day 21 after arthritis induction and persisted for 36 days. The symptoms and molecular mechanisms of CIA and crocin-treated CIA rats were compared and investigated. RESULTS:CIA rats presented severe RA symptoms, including high arthritis score, paw swelling, joint inflammation, bone erosion, chondrocyte death, cartilage destruction, enhanced expressions of matrix metalloproteinase (MMP) and pro-inflammatory cytokines. However, crocin could mitigate these symptoms. Crocin (40?mg/kg) exhibited the most efficient therapeutic function on CIA rats: the histological scores of joint inflammation, bone erosion, chondrocyte death, cartilage surface erosion, and bone erosion of CIA rats receiving 40?mg/kg crocin treatment were comparable to the normal rats. MMP-1, -3 and -13 protein expression levels of CIA rats with 40?mg/kg crocin treatment were decreased to levels similar to normal rats. Moreover, crocin could also inhibit the expression of TNF-?, IL-17, IL-6 and CXCL8 in serum and ankle tissues of CIA rats. CONCLUSIONS:In summary, crocin exhibits therapeutic potential for RA, by mitigating the symptoms and inhibiting the pro-inflammatory factor expression.

| S-EPMC6168764 | biostudies-literature

Suppression of joint pain in transient receptor potential vanilloid 4 knockout rats with monoiodoacetate-induced osteoarthritis.

Project description:IntroductionTransient receptor potential vanilloid 4 (TRPV4) modulates osteoarthritic (OA) pain in animal models. However, the pathophysiological function of TRPV4 in regulating OA pain remains poorly understood.MethodsWe developed TRPV4-knockout (TRPV4-KO) rats and assessed the effects of Trpv4 gene deficiency in a monoiodoacetate (MIA)-induced OA pain model (MIA rats) by examining pain-related behavior, pathological changes, and electrophysiological changes in dorsal root ganglion (DRG) neurons. The changes detected in TRPV4-KO rats were confirmed in wild-type rats using a TRPV4 antagonist.ResultsTransient receptor potential vanilloid 4-KO rats showed the same pain threshold as wild-type rats for thermal or pressure stimuli under normal conditions. Trpv4 gene deletion did not suppress the development of osteoarthritis pathologically in MIA rats. However, the OA-related mechanical pain behaviors observed in MIA rats, including decreased grip strength, increased mechanical allodynia, and reduced weight-bearing on the ipsilateral side, were completely suppressed in TRPV4-KO rats. The DRG neurons in wild-type but not TRPV4-KO MIA rats were depolarized with increased action potentials. Transient receptor potential vanilloid 4 antagonist treatments recapitulated the effects of genetic Trpv4 deletion.ConclusionTransient receptor potential vanilloid 4 was sensitized in the DRG neurons of MIA rats and played a critical role in the development of OA pain. These results suggest that the inhibition of TRPV4 might be a novel potent analgesic strategy for treating OA pain.

| S-EPMC8357256 | biostudies-literature

Matrine Exerts a Strong Anti-Arthritic Effect on Type II Collagen-Induced Arthritis in Rats by Inhibiting Inflammatory Responses.

Project description:To investigate anti-arthritic effects of matrine isolated from the roots of S. flavescens on type II collagen-induced arthritis (CIA) in rats and to explore its related potential mechanisms, CIA rats were established and administered with matrine (20, 40 or 80 mg/kg/days, for 30 days). Subsequently, blood was collected to determine serum levels of TNF-?, IL-1?, IL-6, IL-8, IL-17A, IL-10, MMP-2, MMP-3 and MMP-9, and hind paws and knee joints were collected for histopathological examination. Furthermore, indices of the thymus and spleen were determined, and synovial tissues were collected to determine the protein expressions of p-I?B, I?B, Cox-2 and iNOS. Our results indicated that matrine significantly suppressed inflammatory reactions and synovial tissue destruction. Matrine inhibited paw swelling, arthritis indices and weight loss in CIA rats. Additionally, matrine decreased the levels of TNF-?, IL-1?, IL-6, IL-8, IL-17A, MMP-2, MMP-3 and MMP-9. Matrine also down-regulated expressions of p-I?B, Cox-2, and iNOS but up-regulated I?B in synovial tissues in CIA rats. The results suggested matrine possesses an anti-arthritic effect in CIA rats via inhibiting the release of pro-inflammatory cytokines and proteins that promote the NF-?B pathway.

| S-EPMC5037690 | biostudies-literature

Tolerogenic nanoparticles induce type II collagen-specific regulatory T cells and ameliorate osteoarthritis.

Project description:Local inflammation in the joint is considered to contribute to osteoarthritis (OA) progression. Here, we describe an immunomodulating nanoparticle for OA treatment. Intradermal injection of lipid nanoparticles (LNPs) loaded with type II collagen (Col II) and rapamycin (LNP-Col II-R) into OA mice effectively induced Col II-specific anti-inflammatory regulatory T cells, substantially increased anti-inflammatory cytokine expression, and reduced inflammatory immune cells and proinflammatory cytokine expression in the joints. Consequently, LNP-Col II-R injection inhibited chondrocyte apoptosis and cartilage matrix degradation and relieved pain, while injection of LNPs loaded with a control peptide and rapamycin did not induce these events. Adoptive transfer of CD4+CD25+ T cells isolated from LNP-Col II-R-injected mice suggested that Tregs induced by LNP-Col II-R injection were likely responsible for the therapeutic effects. Collectively, this study suggests nanoparticle-mediated immunomodulation in the joint as a simple and effective treatment for OA.

| S-EPMC9699678 | biostudies-literature

Ginsenoside Rb<sub>1</sub> inhibits monoiodoacetate-induced osteoarthritis in postmenopausal rats through prevention of cartilage degradation.

Project description:BackgroundGinsenoside Rb1 (G-Rb1), one of the major active compounds in Panax ginseng, has already been shown to reduce inflammation in various diseases. Osteoarthritis (OA) has traditionally been considered a degenerative disease with degradation of joint articular cartilage. However, recent studies have shown the association of inflammation with OA. In the present study, we investigated whether Rb1 had an antiinflammatory effect on monoiodoacetate (MIA)-induced OA in ovariectomized rats as a model of postmenopausal arthritis.MethodsG-Rb1 at a dosage of 3 and 10 μg/kg body weight was administered every 3 days intraarticularly for a period of 4 weeks to observe antiarthritic effects. Diclofenac (10 mg/kg) served as a positive control.ResultsThe administration of Rb1 significantly ameliorated OA inflammatory symptoms and reduced serum levels of inflammatory cytokines. Furthermore, G-Rb1 administration considerably enhanced the expression of bone morphogenetic protein-2 and collagen 2A and reduced the levels of matrix metalloproteinase-13 genes, indicating a chondroprotective effect of G-Rb1. G-Rb1 also significantly reduced the expression of several inflammatory cytokines/chemokines (interferon gamma (IFN-γ), monocyte chemoattractant protein-1 (MCP-1)/CCL-2, interleukin [IL]-1β, and IL-6). Histological analysis demonstrated that G-Rb1 significantly attenuated the pathological changes in MIA-induced OA in ovariectomized rats. Safranin O and toluidine blue staining further demonstrated that G-Rb1 effectively prevented the degradation of cartilage and glycosaminoglycans, respectively.ConclusionOverall, our results suggest that G-Rb1 exerts cartilage protective effect on MIA-induced ovariectomized OA rats, by inhibiting inflammatory mediators such as IL-6, IL-1β, MCP-1/CCL-2, cyclooxygenase-2 (COX-2), and prostaglandin E2 (PGE2). These results shed a light on possible therapeutic application of G-Rb1 in OA.

| S-EPMC8020294 | biostudies-literature

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