Search Results (41)

The pathogenesis of knee osteoarthritis (OA) is multifaceted and involves the complete joint microenvironment. Despite beneficial evidence of curcumin, the mechanistic insights of nanoemulsified curcumin (n-Cur) delivery to the knee-OA microenvironment are limited. The study aimed to establish localized delivery of curcumin nanoemulsion in the knee joint of OA rats and to examine detailed histopathological changes. n-Cur was prepared using a neutral dietary oil and a surfactant. Adult (5 mo) male SD rats were intra-articularly delivered 40 mg/mL of monoiodoacetate (MIA) to induce OA in the left knee and further treated with n-Cur (30 mg/mL). The effect of n-Cur on macrophage recruitment was evaluated using a co-culture model of CHON 001 and RAW 264.7 cells. In the MIA model, localized delivery of n-Cur significantly reduced knee joint edema and joint space narrowing in the target site. Curcumin ameliorated cartilage degeneration by reducing fibrillation, hypocellularity, and restoring matrix proteoglycan, as evidenced by histology. Reduced synovial inflammation displays the effect of curcumin on the synovium, possibly by lowering the recruitment of macrophages in chemoattractant-stimulated chondrocytes. Thus, curcumin nanoemulsion can act as a chondroprotective agent, modulating the OA microenvironment by reducing joint edema, synovial inflammation, and oxidative stress in the OA model. Full article

Cartilage regeneration has long been a major challenge in the treatment of osteoarthritis (OA). Aiming to develop a simple outpatient treatment for knee OA, we have demonstrated the potential of combining Nomura’s jellyfish mucin (JM) and hyaluronic acid (HA) to contribute to cartilage repair and regeneration in chondrocytes. In this study, we examined the effects of moon jellyfish JM and jellyfish collagen (JC) on chondrocytes. Polydactyly-derived chondrocytes (PDs), obtained from polydactyly surgery, were used. PDs were cultured in media supplemented with JM or JC, harvested, and evaluated by RT-qPCR. The effects of simultaneous addition of the inflammatory cytokine IL-1β were also examined. Furthermore, the effects on rat articular cartilage were investigated. A mono-iodoacetate (MIA) model was created by intra-articular injection in 6-week-old rats, followed by four intra-articular injections. Evaluations were performed using macroscopic observation and histological assessment with the OARSI scoring system. In vitro, the addition of JM or JC significantly affected the expression of ACAN, MMP3, and ADAMTS5. However, in vivo, intra-articular injection of JM alone did not significantly suppress cartilage degeneration in MIA-induced OA model rats. Both JM and JC may contribute to the suppression of cartilage degeneration as well as to cartilage repair and regeneration, even in the absence of HA. However, further studies are needed to clarify the optimal conditions, such as dosage, timing, and delivery method, that are required to achieve these effects in articular cartilage. Full article

This study investigated the effects of different frequencies of moderate treadmill exercise on a knee osteoarthritis (OA) model in Wistar rats. Sixty male Wistar rats were randomly assigned to four groups: Sham, OA, OA + exercise three times/week (OA + 3×), and OA + exercise five times/week (OA + 5×). OA was induced via intra-articular injection of sodium monoiodoacetate (MIA) in the right knee. Fifteen days post-MIA, exercise treatment began with a one-week adaptation period, followed by eight weeks of aerobic training. Protocols involved treadmill walking (30 min/day) at 13 m/min for the first four weeks and 16 m/min for the last four weeks. At the end, animals were anesthetized and euthanized for collection of intra-articular tissues and gastrocnemius muscle. Both exercise regimens inhibited OA progression; however, OA + 5× yielded more pronounced effects, including greater energy expenditure, weight reduction, oxidative stress modulation, decreased pro-inflammatory and catabolic markers, increased anti-inflammatory and anabolic parameters, reduced injury scores, prevention of cartilage thinning, and increased cartilage surface area. Although both frequencies conferred cartilage protection, moderate exercise five times per week produced superior therapeutic outcomes, suggesting a dose-dependent benefit of exercise in OA management. Full article

Osteoarthritis (OA) is a progressive joint disease that is commonly managed with palliative drugs, many of which are associated with undesirable side effects. This study investigated the therapeutic potential of a novel supplementation with guarana, selenium, and L-carnitine (GSC) in a rat model of chemically induced OA. Forty male Wistar rats (8–9 weeks old) received intra-articular sodium monoiodoacetate (Mia) to induce OA, and were subsequently treated with GSC. Inflammatory and oxidative stress parameters were analyzed at the end of the experiment. GSC supplementation enhanced endogenous antioxidant defenses, suggesting systemic antioxidant activity. However, no histological improvement was observed. In silico analyses indicated that Mia-induced OA may involve a complex molecular environment that GSC, at the tested dose, failed to modulate at the site of injury. Despite the limited local effects, these findings support the systemic benefits of GSC and highlight the potential of natural compound-based strategies in OA management. Given the adverse effects of conventional pharmacotherapy, the development of alternative, naturally derived treatments remains a promising avenue for future research. Full article

In chlorination disinfection treatment, residual iodinated X-ray contrast media (ICMs) are the precursors to iodinated disinfection by-products (I-DBPs). This study employed CoFe₂O₄ nanoparticle catalytic peracetic acid oxidation (CoFe₂O₄/PAA) to remove iopamidol (IPM) and control I-DBP formation. The experimental results demonstrated that over 90% of the IPM degradation was achieved in 40 min. The metastable intermediate (≡Co(II)-OO(O)CCH₃), rather than the alkoxyl radicals, was identified as the dominant oxidation species (ROS). The electron transfer pathways between the metastable intermediate and IPM were oxygen-atom transfer and single-electron transfer. The monoiodoacetic acid formation potential (MIAAFP) was investigated. In ultraviolet-activated ClO⁻ (UV/chlorine), a portion of I⁻ generated through IPM dehalogenation underwent conversion to reactive iodine species (RIS), consequently elevating the MIAAFP. In CoFe₂O₄/PAA, the MIAAFP was less than 43% of that in UV/chlorine, which can be attributed to the complete conversion of I⁻ into iodate IO₃⁻ without generating RIS. CoFe₂O₄/PAA is thus a promising treatment for removing ICMs and controlling I-DBP formation due to the efficient degradation of ICMs while avoiding the generation of RIS. Full article

Knee osteoarthritis (OA) often causes chronic pain that disproportionately affects females. Proinflammatory cytokines TNF-α, IL-1β, and IL-6 are key effectors of OA pathological changes. Green light shows potential as an alternative intervention for various pain conditions. However, no studies have investigated green light′s analgesic effects in both sexes in chronic knee OA. We induced unilateral knee OA with intra-articular injection of monoiodoacetate (MIA) in male and female Sprague-Dawley rats. Two days post-injection, the rats were exposed to green-light-emitting diodes (GLED) or ambient room light eight hours daily for 24 days. Knee mechanical sensitivity was assessed using a small animal algometer. Blood serum concentrations of TNF-α, IL-1β, IL-6, and IL-10 were quantified at baseline and 23 days post-injection. MIA injection decreased the knee mechanical thresholds of the male and female rats. GLED exposure attenuated mechanical hypersensitivity in both sexes compared to the controls; however, GLED-induced analgesia occurred sooner and with greater magnitude in males than in females. In both sexes, the analgesic effects of green light lasted 5 days after the final GLED session. Finally, GLED exposure reversed the elevation of serum proinflammatory cytokines. These findings suggest that GLED exposure reduces primary hyperalgesia in OA, potentially by lowering proinflammatory cytokines, and indicate sex differences in GLED-induced analgesia. Full article

Pain is the primary clinical indication of osteoarthritis (OA), and behavioral assessments in rodent pain models are widely used to understand pain patterns. These preclinical pain assessments can also help us to understand the effectiveness of emerging therapeutics for prolonged OA pain management. Along with evoked methods like mechanical allodynia and thermal hyperalgesia, non-evoked methods such as dynamic weight bearing (DWB) analysis are valuable tools for behavioral assessments of pain. Both these methods were utilized to study pain-induced behavioral changes in a monoiodoacetate (MIA)-induced osteoarthritic pain model, which is a well-established preclinical OA pain model. However, the utility of DWB analysis as an indicator of long-term pain sensitivity (more than 4 weeks) remains largely unexplored. Understanding the long-term sensitivity of DWB is valuable to study the effectiveness of novel prolonged pain-relieving therapeutics. Here, we studied the dynamic behavioral changes in MIA-induced OA rats over a period of 16 weeks using DWB measurements. Female Sprague Dawley rats were injected in the right knee joint with MIA (3 mg) using X-ray guidance. Multiple dynamic postural evaluations such as ipsilateral weight percentage, paw area, contralateral/ipsilateral weight ratio and area ratio were assessed to understand the behavioral changes. The data showed that the ipsilateral weight bearing percentage alone is not sufficient to assess pain-related behavior beyond 6 weeks. This study shows the advantages and limitations of dynamic weight bearing as an assessment tool for the long-term progression of pain behavior in MIA-induced OA rats. Full article

Osteoarthritis (OA) is a chronic degenerative disease leading to articular cartilage destruction. Menopausal and postmenopausal women are susceptible to both OA and osteoporosis. S-equol, a soy isoflavone-derived molecule, is known to reduce osteoporosis in estrogen-deficient mice, but its role in OA remains unknown. This study aimed to explore the effect of S-equol on different degrees of menopausal OA in female Sprague–Dawley (SD) rats induced by estrogen deficiency caused by bilateral ovariectomy (OVX) combined with intra-articular injection of mono-iodoacetate (MIA). Knee joint histopathological change; serum biomarkers of bone turnover, including N-terminal propeptide of type I procollagen (PINP), C-terminal telopeptide of type I collagen (CTX-I) and N-terminal telopeptide of type I collagen (NTX-I); the cartilage degradation biomarkers hyaluronic acid (HA) and N-terminal propeptide of type II procollagen (PIINP); and the matrix-degrading enzymes matrix metalloproteinases (MMP)-1, MMP-3 and MMP-13, as well as the oxidative stress-inducing molecules nitric oxide (NO) and hydrogen peroxide (H₂O₂), were assessed for evaluation of OA progression after S-equol supplementation for 8 weeks. The results showed that OVX without or with MIA injection induced various severity levels of menopausal OA by increasing pathological damage, oxidative stress, and cartilage matrix degradation to various degrees. Moreover, S-equol supplementation could significantly reduce these increased biomarkers in different severity levels of OA. This indicates that S-equol can lessen menopausal OA progression by reducing oxidative stress and the matrix-degrading enzymes involved in cartilage degradation. Full article

Iron oxide nanoparticles (IONPs) represent an important advance in the field of medicine with application in both diagnostic and drug delivery domains, offering a therapeutic approach that effectively overcomes physical and biological barriers. The current study aimed to assess whether oral administration of salicylic acid-functionalized iron oxide nanoparticles (SaIONPs) may exhibit beneficial effects in alleviating histological lesions in a murine monoiodoacetate (MIA) induced knee osteoarthritis model. In order to conduct our study, 15 Wistar male rats were randomly distributed into 3 work groups: Sham (S), MIA, and NP. At the end of the experiments, all animals were sacrificed for blood, knee, and liver sampling. Our results have shown that SaIONPs reached the targeted sites and also had a chondroprotective effect represented by less severe histological lesions regarding cellularity, altered structure morphology, and proteoglycan depletion across different layers of the knee joint cartilage tissue. Moreover, SaIONPs induced a decrease in malondialdehyde (MDA) and circulating Tumor Necrosis Factor-α (TNF-α) levels. The findings of this study suggest the therapeutic potential of SaIONPs knee osteoarthritis treatment; further studies are needed to establish a correlation between the administrated dose of SaIONPs and the improvement of the morphological and biochemical parameters. Full article

Osteoarthritis (OA) is a pathology of great impact worldwide. Its physiopathology is not completely known, and it is usually diagnosed by imaging techniques performed at advanced stages of the disease. The aim of this study was to evaluate early serum metabolome changes and identify the main metabolites involved in an inflammatory OA animal model. This study was performed on thirty rats. OA was induced in all animals by intra-articular injection of monoiodoacetate into the knee joint. Blood samples were taken from all animals and analyzed by mass spectrometry before OA induction and 28, 56, and 84 days following induction. Histological evaluation confirmed OA in all samples. The results of this study allow the identification of several changes in 18 metabolites over time, including organic acids, benzenoids, heterocyclic compounds, and lipids after 28 days, organic acids after 56 days, and lipid classes after 84 days. We conclude that OA induces serological changes in the serum metabolome, which could serve as potential biomarkers. However, it was not possible to establish a relationship between the identified metabolites and the time at which the samples were taken. Therefore, these findings should be confirmed in future OA studies. Full article

The objective of this study was to investigate the effect of low-molecular-weight fish collagen (valine-glycine-proline-hydroxyproline-glycine-proline-alanine-glycine; LMWCP) on H₂O₂- or LPS-treated primary chondrocytes and monoiodoacetate (MIA)-induced osteoarthritis rat models. Our findings indicated that LMWCP treatment exhibited protective effects by preventing chondrocyte death and reducing matrix degradation in both H₂O₂-treated primary chondrocytes and cartilage tissue from MIA-induced osteoarthritis rats. This was achieved by increasing the levels of aggrecan, collagen type I, collagen type II, TIMP-1, and TIMP-3, while simultaneously decreasing catabolic factors such as phosphorylation of Smad, MMP-3, and MMP-13. Additionally, LMWCP treatment effectively suppressed the activation of inflammation and apoptosis pathways in both LPS-treated primary chondrocytes and cartilage tissue from MIA-induced osteoarthritis rats. These results suggest that LMWCP supplementation ameliorates the progression of osteoarthritis through its direct impact on inflammation and apoptosis in chondrocytes. Full article

Knee osteoarthritis (KOA), one of the most common orthopedic disorders concerning the adult population worldwide, is a condition characterized by progressive destruction of the articular cartilage and the presence of an inflammatory process. The aim of our study was to assess whether nicotinamide riboside (NR), a popular anti-aging supplement, can reduce the rate of cartilage destruction and alleviate the inflammatory response compared to the commonly prescribed collagen supplement in a murine monoiodoacetate (MIA)-induced KOA model. Twenty Wistar rats were randomly assigned to 4 groups: sham (S), MIA and NR, MIA and hydrolyzed collagen (HC), and MIA. At the end of the experiment, the right knees and blood samples were collected for histological assessment and biochemical evaluation of nitric oxide, malondialdehyde, total antioxidant capacity, reduced glutathione, glutathione peroxidase, superoxide dismutase, catalase, myeloperoxidase, and tumoral necrosis factor-alpha (TNF-α). The study determined that the treatment with NR in a similar dose with HC decreased blood/serum levels of oxidative stress biomarkers and the histological lesions in almost the same manner. The present findings suggest that NR may exhibit chondroprotective and anti-inflammatory effects in MIA-induced KOA in rats. Full article

During the COVID-19 (coronavirus disease 2019) outbreak, many people were infected, and the symptoms may persist for several weeks or months for recovering patients. This is also known as “long COVID” and includes symptoms such as fatigue, joint pain, muscle pain, et cetera. The COVID-19 virus may trigger hyper-inflammation associated with cytokine levels in the body. COVID-19 can trigger inflammation in the joints, which can lead to osteoarthritis (OA), while long-term COVID-19 symptoms may lead to joint damage and other inflammation problems. According to several studies, sesame has potent anti-inflammatory properties due to its major constituent, sesamin. This study examined sesamin’s anti-inflammatory, anti-osteoarthritis, and anti-COVID-19 effects. Moreover, in vivo and in vitro assays were used to determine sesamin’s anti-inflammatory activity against the RAW264.7 and SW1353 cell lines. Sesamin had a dose-dependent effect (20 mg/kg) in a monoiodoacetic acid (MIA)-induced osteoarthritis rat model. Sesamin reduced paw swelling and joint discomfort. In addition, the findings indicated that sesamin suppressed the expression of iNOS (inducible nitric oxide synthase) and COX-2 (cyclooxygenase-2) in the RAW264.7 cell line within the concentration range of 6.25–50 μM. Furthermore, sesamin also had a suppressive effect on MMP (matrix metalloproteinase) expression in chondrocytes and the SW1353 cell line within the same concentration range of 6.25–50 μM. To examine the anti-viral activity, an in silico analysis was performed to evaluate sesamin’s binding affinity with SARS-CoV-2 RdRp (severe acute respiratory syndrome coronavirus 2 RNA-dependent RNA polymerase) and human ACE2 (angiotensin-converting enzyme 2). Compared to the controls, sesamin exhibited strong binding affinities towards SARS-CoV-2 RdRp and human ACE2. Furthermore, sesamin had a higher binding affinity for the ACE2 target protein. This study suggests that sesamin shows potential anti-SARS-CoV-2 activity for drug development. Full article

Osteoarthritis (OA) is one of the most prevalent diseases of the osteoarticular system. Progressive destruction of joints is accompanied by development of pathological changes in the muscle tissue, i.e., weakening, atrophy, and remodelling (sarcopenia). The aim of the present study is to assess the impact of physical activity on the musculoskeletal system in an animal model of early degenerative lesions in the knee joint. The study involved 30 male Wistar rats. The animals were allocated to three subgroups of 10 animals each. Each animal from the three subgroups received sodium iodoacetate by injection into the patellar ligament of the right knee joint, whereas saline was administered through the patellar ligament in the left knee joint. The rats in the first group were stimulated to exercise on a treadmill. The animals in the second group were allowed to lead a natural lifestyle (no treadmill stimulation). In the third group, all parts of the right hind limb muscle were injected with Clostridium botulinum toxin type A. The study demonstrated that, compared to the active rats, bone density in the immobilised rats decreased, as indicated by the densitometric assessment of the whole body and the examination of rats’ hind limbs and knee joints alone. This clearly evidenced the impact of physical activity on bone mineralisation. The weight of both fat and muscle tissues in the physically inactive rats was reduced. Additionally, the adipose tissue had higher weight in the entire right hind limbs, where monoiodoacetic acid was administered to the knee joint. The animal model clearly showed the importance of physical activity in the early stages of OA, as it slows down the process of joint destruction, bone atrophy, and muscle wasting, whereas physical inactivity contributes to progression of generalised changes in the musculoskeletal system. Full article

The racemic mixture dimiracetam negatively modulates NMDA-induced glutamate release in rat spinal cord synaptosomal preparations and is orally effective in models of neuropathic pain. In this study, we compared the effects of dimiracetam, its R- or S-enantiomers, and the R:S 3:1 non-racemic mixture (MP-101). In vitro, dimiracetam was more potent than its R- or S-enantiomers in reducing the NMDA-induced [³H]D-aspartate release in rat spinal cord synaptosomes. Similarly, acute oral administration of dimiracetam was more effective than a single enantiomer in the sodium monoiodoacetate (MIA) paradigm of painful osteoarthritis. Then, we compared the in vitro effects of a broad range of non-racemic enantiomeric mixtures on the NMDA-induced [³H]D-aspartate release. Dimiracetam was a more potent blocker than each isolated enantiomer but the R:S 3:1 non-racemic mixture (MP-101) was even more potent than dimiracetam, with an IC₅₀ in the picomolar range. In the chronic oxaliplatin-induced neuropathic pain model, MP-101 showed a significantly improved anti-neuropathic profile, and its effect continued one week after treatment suspension. MP-101 also performed better than dimiracetam in animal models of cognition and depression. Based on the benign safety and tolerability profile previously observed with racemic dimiracetam, MP-101 appears to be a novel, promising clinical candidate for the prevention and treatment of several neuropathic and neurological disorders. Full article