Search Results (93)

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

The pathogenesis of temporomandibular joint osteoarthritis (TMJOA) is poorly understood. This study aims to identify key biomarkers involved in TMJOA progression and explore potential therapeutic drugs through transcriptome analysis. A rat TMJOA model was established by bilateral injection of monosodium iodoacetate (MIA) into the TMJ cavities. Model validation was conducted using hematoxylin-eosin (HE) and Safranin O-Fast Green (SO-FG) staining. Differentially expressed genes (DEGs) were identified through RNA sequencing. Key pathways were explored using Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), and Reactome pathway analyses. DEGs were clustered using MCODE analysis, and Hexokinase 3 (HK3) was identified as a key gene, which was further validated by qPCR. Potential drugs targeting HK3 were selected using the DGIdb database, and molecular docking was conducted to confirm drug-HK3 binding affinity. The TMJOA model was successfully established. RNA-seq analysis revealed 160 upregulated and 97 downregulated DEGs. KEGG, GO, and Reactome pathways analysis identified dysregulated pathways. The top five clusters of DEGs were identified, with HK3 emerging as the key gene. qPCR validation confirmed upregulated HK3 mRNA expression in TMJOA cartilage compared to the control group. Three drugs (MK8719, LY3372689, and Thiamet-G) targeting HK3 were identified through the Drug-Gene Interaction Database (DGIdb) screening, and molecular docking demonstrated high binding affinity between these drugs and HK3. This study suggests that HK3 may play a role in TMJOA progression and could serve as a potential biomarker for inflammatory progression in TMJOA. Targeting HK3 may offer new diagnostic and therapeutic strategies for TMJOA management. Full article

Background/Objectives: Osteoarthritis (OA) is a progressive joint disease characterized by inflammation, cartilage degradation, and subchondral bone changes, for which effective disease-modifying therapies are lacking. Messenger RNA (mRNA)-based therapeutics offer a versatile approach to modulate joint pathology, but their application to OA remains limited. Methods: We evaluated intra-articular delivery of therapeutic mRNAs using polyplex nanomicelles, a non-inflammatory and minimally invasive carrier system, in a rat model of inflammation-driven OA induced by monosodium iodoacetate (MIA). Results: IL-1 receptor antagonist (IL-1Ra) mRNA reduced synovial inflammation and alleviated pain and swelling. RUNX1 mRNA, a transcription factor critical for chondrogenesis, supported chondrocyte viability, type II collagen expression, and cartilage structure. Under conditions of pronounced inflammation, however, the protective effects of RUNX1 mRNA alone were modest. Notably, combined administration of IL-1Ra and RUNX1 mRNAs produced synergistic therapeutic benefits, with enhanced chondroprotection and preservation of subchondral bone integrity. Conclusions: These findings suggest that while RUNX1 is essential for maintaining cartilage homeostasis, effective control of joint inflammation is required for its therapeutic activity. Dual mRNA therapy delivered by polyplex nanomicelles therefore represents a promising strategy to address the multifactorial pathology of OA. 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

Background/Objectives: Osteoarthritis is a degenerative joint disease that affects people worldwide. It is characterized by joint pain, synovial inflammation, and the degradation of articular cartilage with subchondral bone. Presently, there is no known cure, and pharmacological treatment options are limited. Blueberries contain phytochemicals, which have been linked to positive health benefits and may offer therapeutic benefits. Therefore, the purpose of this study was to examine the dose-dependent effects of whole blueberries on arthritis symptoms in a monosodium iodoacetate (MIA)-induced rat model of osteoarthritis. Methods: Forty female rats were used for this study. Thirty were injected with MIA to induce joint degradation associated with osteoarthritis. Ten served as controls without MIA induction. The MIA-induced rats were randomized into three groups. All groups were fed a casein-based diet, with two of the MIA-induced groups receiving an addition of whole-blueberry powder at 5% and 10%. Fasted blood specimens and tissues of interest were collected post-euthanasia for analysis. Mechanical allodynia and joint widths were assessed throughout this study. Results: MIA induction resulted in changes in pain behaviors and the development of mechanical allodynia. The MIA injection produced inflammation, pain symptoms, and behaviors that are representative of those observed in humans with osteoarthritis. The incorporation of whole blueberries into diets reduced pain behaviors and inflammation. Conclusions: Overall, whole blueberries showed limited, non-dose-dependent effects in the MIA-induced rat model of osteoarthritis. While some outcomes improved in blueberry-treated groups, the overall results were not consistently significant. These preliminary findings suggest potential biological activity and support the further investigation of blueberries’ therapeutic efficacy. Full article

BYVET JOINT HEAL^TM (BJH) contains mucopolysaccharide protein, chondroitin sulfate, type II collagen, and omega-3 fatty acids, which protect and prevent osteoarthritis (OA)-associated tissue damage and degradation in dogs and cats. This study aimed to generate a novel dietary supplement and evaluate its prevention and therapeutic efficacy in an OA Sprague Dawley rat model induced using monosodium iodoacetate (MIA). Negative control, MIA-induced OA control (MIA), OA rats treated with BJH three weeks after (M+BJH3) and those treated two weeks before and three weeks after OA induction (BJH2+M+BJH3) groups were assigned. M+BJH3 and BJH2+M+BJH3 had similar mean body weight increases until 29 days. BJH2+M+BJH3 showed a significantly higher body weight than M+BJH3 and MIA on the final day. Interleukin-1β in BJH2+M+BJH3 was significantly lower than that in MIA. Tumor necrosis factor-α, aggrecan, matrix metalloproteinases13, and cyclooxygenase-2 levels in M+BJH3 and BJH2+M+BJH3 significantly differed compared to those in MIA. BJH administration before OA induction significantly decreased OA severity and functional recovery. Consuming a BJH supplement showed modifying and chondroprotective effects and significantly reduced cartilage degeneration and inflammation with no side effects. Hence, our findings demonstrate the potential of using BJH as a safe therapeutic and preventive supplement for OA and associated cartilage abnormalities. Also, 30 dogs diagnosed with OA by a veterinarian participated in the clinical trial, and BJH was provided for 8 weeks. Blood tests (CBC, serum chemistry) and joint assessment were performed before and after the feeding, and the effects of a BJH supplement were compared. BJH supplement was easy to administer, and no side effects were reported. Feeding BJH supplementation alone to dogs with arthritis had an overall positive effect on arthritis scores for 8 weeks without any other treatment, including non-steroidal drugs. Full article

Maternal immune activation (MIA)—infection with an immunogen during pregnancy—is linked to an increased risk of neurodevelopmental disorders (NDDs) in offspring. Both MIA and NDDs are associated with developmental delays in offsprings’ motor behavior. Therefore, the current study examined the effects of MIA on neonatal reflex development in male and female offspring. Sprague Dawley rats were administered lipopolysaccharide (LPS; 50 μg/mL/kg, i.p.) or saline on embryonic day (E)15 of gestation. The offspring were then tested daily from postnatal day (P)3–P21 to determine their neonatal reflex abilities. The maternal care behaviors of the dam were also quantified on P1–P5, P10, and P15. We found that, regardless of sex, the E15 LPS offspring were able to forelimb grasp, cliff avoid, and right with a correct posture at an earlier postnatal age than the E15 saline offspring did. The E15 LPS offspring also showed better performance of forelimb grasping, hindlimb grasping, righting with correct posture, and walking with correct posture than the E15 saline offspring did. There were no significant differences in maternal licking/grooming, arched-back nursing, non-arched-back nursing, or total nursing across the E15 groups. Overall, these findings suggest that MIA with LPS on E15 accelerates reflex development in offspring without affecting maternal care. This may be explained by the stress acceleration hypothesis, whereby early-life stress accelerates development to promote survival. Full article

Osteoarthritis (OA) is a chronic disease characterized by cartilage degradation, leading to bone friction, inflammation, stiffness, pain, and reduced mobility. This study investigates the therapeutic effects of porcine-derived chondroitin sulfate sodium (CS) on OA symptoms at both cellular and animal levels. In vitro study, HTB-94 chondrocytes were treated with inflammatory stimuli and CS (10, 50, 100, and 200 μg/mL) to assess the release of inflammatory mediators and the expression of genes and proteins related to cartilage synthesis and degradation. In vivo study, an MIA-induced OA rat model was used, and CS (62, 124, and 248 mg/kg b.w.) was orally administered for 4 weeks. Key parameters, such as exercise capacity, micro-CT, histological evaluation of joint tissues, serum inflammatory markers, and the expression of mRNA and proteins (inflammatory, cartilage synthesis and degradation, and apoptosis markers), were analyzed. Porcine-derived CS significantly reduced PGE₂, NO, and extracellular matrix degradation marker (COMP and CTX-II) levels and increased the expression of cartilage synthesis-related genes and proteins in both HTB-94 cells and the MIA-induced rats. Additionally, CS modulated cartilage degradation pathways and notably inhibited apoptosis in vivo. The effects of porcine CS were comparable to the NSAID ibuprofen, demonstrating its potential as an anti-inflammatory and chondroprotective agent for OA management and dietary supplementation. Full article

Background: Osteoarthritis (OA) is a chronic condition characterized by joint pain and disability, driven by excessive oxidative stress and inflammatory cytokine production in chondrocytes, resulting in cell death and cartilage matrix breakdown. Our previous study showed that in monosodium iodoacetate (MIA)-induced OA rats, oral administration of heat-killed Lactobacillus delbrueckii subsp. lactis 557 (LDL557) could significantly decrease OA progression. Methods: Accordingly, we designed an in vitro cell culture study aimed at investigating the effects of heat-killed LDL557 extracts on chondrocytes using SW1353 cells (a human chondrosarcoma cell line) challenged with 5 μM MIA to mimic OA conditions. Results: The results showed that the 10 μg/mL LDL557 extracts protected SW1353 cells from MIA-induced death and reduced extracellular matrix (ECM) loss, as evaluated by toluidine blue O staining and extracellular matrix component synthesis with RT-qPCR measurement. This was achieved by decreasing the expression of MIA-induced pro-inflammatory cytokines, including IL-1β, IL-6, and TNF-α, while slightly increasing the MIA-suppressed expression of the anti-inflammatory cytokine IL-10, which were evidenced by RT-qPCR analysis. Moreover, the RT-qPCR evaluation also indicated that the LDL557 extracts slightly reduced the expression of COX-2 compared with the control, while it did not reduce the MIA-increased expression of microsomal prostaglandin E synthase-1 (mPGES-1). In addition, the LDL557 extracts influenced neither the matrix-degrading protease expressions measured via RT-qPCR nor the oxidative stress measured via fluorescence flow cytometry in the cells with or without the MIA challenge. Conclusions: This study demonstrates that LDL557 extracts may protect chondrocytes from OA damage by reducing inflammation-related factors and thus mitigating cartilage matrix loss, suggesting LDL557 extracts are attractive alternatives for OA applications. Full article

Background: Osteoarthritis (OA) is a common degenerative joint condition caused by an imbalance between cartilage synthesis and degradation, which disrupts joint homeostasis. This study investigated the anti-inflammatory and joint-improving effects of Pinus densiflora root extract powder (PDREP) in both in vitro and in vivo OA models. Methods/Results: In an in vitro OA model, in which SW1353 human chondrosarcoma cells were treated with interleukin (IL)-1β, PDREP treatment significantly reduced the mRNA levels of matrix metalloproteinase (MMP)-1, MMP-3, and MMP-13 while enhancing collagen type II alpha 1 (Col2a1) mRNA level, and decreased IL-6 and prostaglandin E2 (PGE2) levels. In addition, PDREP inhibited the phosphorylation of extracellular signal-regulated kinases (ERK), c-Jun N-terminal kinase (JNK), p38, nuclear factor-kappa B (NF-κB), and the expression of inducible nitric oxide synthase (iNOS). In a monosodium iodoacetate (MIA)-induced OA rat model, the administration of PDREP resulted in decreased OA clinical indices, improved weight-bearing indices and gait patterns, reduced histological damage, and lowered serum inflammatory cytokine and MMPs expression. Furthermore, PDREP downregulated the phosphorylation of ERK, JNK, p38, and NF-κB, as well as the expression of iNOS, consistent with the in vitro findings. Conclusions: These results suggest that PDREP exhibits anti-inflammatory and joint-improving effects and has potential as a therapeutic strategy or functional food for the treatment of OA. Full article

Osteoarthritis is a chronic inflammatory condition characterized by the degeneration of joint cartilage and underlying bone, resulting in pain, swelling, and reduced mobility. This study evaluates the efficacy of salmon nasal cartilage-derived proteoglycans in mitigating osteoarthritis symptoms and investigates the underlying molecular mechanisms. This study employed a rat model of osteoarthritis induced by monosodium iodoacetate (MIA) injection. The rats were orally administered salmon nasal cartilage-derived proteoglycans or ibuprofen. Key aspects of osteoarthritis pathology, including impaired exercise ability, inflammation, extracellular matrix degradation, and chondrocyte apoptosis, were assessed using histological analysis, micro-CT, treadmill testing, serum assays, and mRNA/protein expression studies. The MIA injection caused significant cartilage damage, reduced bone mineral density, and impaired exercise ability. Additionally, it elevated serum levels of prostaglandin E2 and nitric oxide, increased the mRNA and protein levels of inflammation-related factors, and activated apoptosis signaling pathways in cartilage. Treatment with salmon nasal cartilage-derived proteoglycans significantly improved cartilage morphology and mineralization, reduced inflammation, and inhibited apoptosis signaling pathways, with effects comparable to those observed with ibuprofen treatment. These findings highlight the potential of salmon nasal cartilage-derived proteoglycans as a therapeutic agent for managing osteoarthritis by effectively reducing inflammation, preventing cartilage degradation, and inhibiting chondrocyte apoptosis. 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

Low-grade body inflammation is a major cause of osteoarthritis (OA), a common joint disease. Gut dysbiosis may lead to systemic inflammation which can be prevented by probiotic administration. The Lactobacillus delbrueckii subsp. lactis 557 (LDL557) has been demonstrated to have beneficial effects for anti-inflammation. This study investigated the effects of LDL557 on OA progress using monosodium iodoacetate (MIA)-induced OA of rats. Live or heat-killed (HK)-LDL557 of a low or high dose was administrated for two weeks before MIA-induced OA, and then continuously administrated for another six weeks. After taking supplements for eight weeks, OA progress was analyzed. Results showed that MIA induced knee joint swelling, chondrocyte damage, and cartilage degradation, and supplementation with a high dose of LDL557 reduced MIA-induced knee joint swelling, chondrocyte damage, and cartilage degradation. Additionally, MIA increased serum levels of the matrix-degrading enzyme MMP-13, while a high dose of HK-LDL557 decreased it for the controls. Simultaneously, bone turnover markers and inflammatory cytokines of serum were assayed, but no significant differences were found except for a TNF-α decrease from a low dose of live LDL557. These results demonstrated that supplementation with high doses of live LDL557 or HK-LDL557 can reduce the progression of MIA-induced OA in rats. 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