Search Results (128)

Background and Objectives: Osteoarthritis (OA) is a degenerative joint disease involving inflammation, oxidative stress, and extracellular matrix (ECM) degradation, leading to cartilage damage and joint dysfunction. This study aimed to evaluate the chondroprotective effects of intra-articular hydrolyzed collagen in a rat model of knee OA using a dual-compartment biochemical and histological approach. Materials and Methods: Twenty male Sprague-Dawley rats underwent ACL transection to induce osteoarthritis and were randomly assigned to receive intra-articular hydrolyzed collagen or saline once weekly for three weeks. At six weeks, knee joints were evaluated histologically using the Mankin score. Synovial fluid and cartilage homogenates were analyzed via enzyme-linked immunosorbent assay (ELISA) for cytokines, cartilage degradation markers, and oxidative stress indicators. Results: The collagen-treated group demonstrated significantly lower Mankin scores. Levels of pro-inflammatory cytokines, interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α), as well as cartilage degradation markers, matrix metalloproteinase-13 (MMP-13), C-terminal crosslinked telopeptide of type II collagen (CTX-II), and cartilage oligomeric matrix protein (COMP), were significantly reduced (p < 0.05). Additionally, oxidative stress indicators including inducible nitric oxide synthase (iNOS), total oxidant status (TOS), and oxidative stress index (OSI) were decreased, while total antioxidant status (TAS) was increased in both synovial fluid and cartilage homogenates (p < 0.05). Conclusions: Intra-articular hydrolyzed collagen reduced inflammation, oxidative stress, and extracellular matrix (ECM) degradation, indicating potential chondroprotective effects across both synovial and cartilage compartments. Full article

In vitro cartilage explant culture has been used to assess nutraceuticals on cartilage responses to inflammatory stimuli. However, applying extracts of nutraceuticals directly to cartilage explants does not account for effects of digestion and hepatic biotransformation, or selective exclusion of product metabolites from joint fluid by the synovial membrane. The current study produced a simulated biological extract of a common nutraceutical (glucosamine; G_sim) by exposing it to a simulated upper gastrointestinal tract digestion, hepatic biotransformation by liver microsomes, and purification to a molecular weight cut-off of 50 kDa. This extract was then used to condition cartilage explants cultured for 120 h in the presence or absence of an inflammatory stimulus (lipopolysaccharide). Media samples were analyzed for prostaglandin E₂ (PGE₂), glycosaminoglycan (GAG), and nitric oxide (NO). Tissue was digested and analyzed for GAG content and stained for viability. Conditioning of explants with G_sim significantly reduced media GAG in stimulated and unstimulated explants and reduced nitric oxide production in unstimulated explants. These data provide evidence for the value of glucosamine in protecting cartilage from deterioration following an inflammatory challenge, and the model improves applicability of these in vitro data to the in vivo setting. Full article

Osteoarthritis (OA) remains a major contributor to pain and disability; however, the current management is largely reactive, focusing on symptoms rather than preventing irreversible cartilage loss. This review first examines the mechanistic foundations for pharmacological chondroprotection—illustrating how conventional agents, such as glucosamine sulfate and chondroitin sulfate, can potentially restore extracellular matrix (ECM) components, may attenuate catabolic enzyme activity, and might enhance joint lubrication—and explores the delivery challenges posed by avascular cartilage and synovial diffusion barriers. Subsequently, a practical “What–How–When” framework is introduced to guide community pharmacists in risk screening, DMOAD selection, chronotherapeutic dosing, safety monitoring, and lifestyle integration, as exemplified by the CHONDROMOVING infographic brochure designed for diverse health literacy levels. Building on these strategies, the P4–4P Chondroprotection Framework is proposed, integrating predictive risk profiling (physicians), preventive pharmacokinetic and chronotherapy optimization (pharmacists), personalized biomechanical interventions (physiotherapists), and participatory self-management (patients) into a unified, feedback-driven OA care model. To translate this framework into routine practice, I recommend the development of DMOAD-specific clinical guidelines, incorporation of chondroprotective chronotherapy and interprofessional collaboration into health-professional curricula, and establishment of multidisciplinary OA management pathways—supported by appropriate reimbursement structures, to support preventive, team-based management, and prioritization of large-scale randomized trials and real-world evidence studies to validate the long-term structural, functional, and quality of life benefits of synchronized DMOAD and exercise-timed interventions. This comprehensive, precision-driven paradigm aims to shift OA care from reactive palliation to true disease modification, preserving cartilage integrity and improving the quality of life for millions worldwide. Full article

(1) Background: Knee osteoarthritis (KOA) induces pain, stiffness, and impaired mobility, particularly in aging populations. Despite providing symptom relief, the long-term efficacy of intra-articular hyaluronic acid (HA) injections remains unclear. With its longer intra-articular residence time and potential chondroprotective effects, porcine-derived atelocollagen is an alternative to HA. We aimed to compare the safety and efficacy of collagen versus HA injections in symptomatic KOA. (2) Methods: This retrospective observational study included 40 patients with KOA who received either two cycles of collagen or HA injections at 6-month intervals. Clinical outcomes were assessed using the visual analog scale (VAS) and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at baseline and 6 months after the first and second injections (Cycle 1 and Cycle 2, respectively). Patient satisfaction and adverse events were recorded. Non-inferiority analysis was conducted for VAS and WOMAC score changes. (3) Results: Significant intragroup improvements in VAS and WOMAC scores were noted after each injection cycle (p < 0.05), albeit without significant between-group differences, non-inferiority of collagen to HA based on predefined margins, and comparable patient-reported satisfaction (>85% reported improvement after each cycle), with similar incidence of mild adverse events (collagen: 20%, HA: 25%, p = 0.705). (4) Conclusions: Intra-articular collagen injections were clinically non-inferior to HA in reducing pain and improving function in patients with KOA across two treatment cycles. Given its favorable safety profile and potential structural benefits, collagen may serve as a viable alternative injectable therapy for the non-surgical management of KOA. 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

Osteoarthritis (OA) is a prevalent and debilitating joint disorder that affects a substantial proportion of the global population, underscoring the urgent need for therapeutic strategies that extend beyond symptomatic management. Although mesenchymal stem cells (MSCs) have emerged as a promising therapeutic modality, their clinical application remains constrained by several inherent limitations. This study explores a cell-free alternative by investigating the therapeutic potential of exosomes derived from bone marrow (BMSCs), adipose tissue (ADSCs), and umbilical cord (UMSCs) MSCs in mitigating OA pathogenesis, utilizing both in vitro and ex vivo models. Exosomes from each MSC source were isolated and characterized through nanoparticle tracking analysis, transmission electron microscopy, and Western blotting to confirm their identity and purity. Subsequently, their chondroprotective, anti-inflammatory, and regenerative properties were systematically assessed through evaluations of cell viability, expression profiles of inflammatory and chondroprotective markers, and chondrocyte migration assays. The results demonstrate that all three types of MSC-derived exosomes (MSC-Exos) exhibit low cytotoxicity while significantly suppressing proinflammatory markers and enhancing the expression of chondroprotective genes. Notably, BMSC-Exos and UMSC-Exos displayed superior efficacy in attenuating inflammation, promoting cartilage protection, and inhibiting chondrocyte apoptosis. Furthermore, all MSC-Exos markedly enhanced chondrocyte motility, a critical component of cartilage repair. Collectively, these findings support the therapeutic promise of MSC-Exos, particularly those derived from BMSCs and UMSCs, as a targeted, cell-free approach for the treatment of OA compared to ADSCs. By modulating inflammation, promoting cartilage regeneration, and preventing chondrocyte apoptosis, MSC-Exos may serve as a viable and scalable alternative to current MSC-based therapies for this widespread degenerative disease. Full article

Knee osteoarthritis (OA) is a common degenerative joint disease affecting global health. Its increasing prevalence, particularly among aging populations, remains a leading cause of disability. Besides conventional pharmacological and surgical treatments, dietary interventions are promising strategies to alleviate OA symptoms and progression. Unfortunately, scientific evidence does not support many commonly used, misleading ideas about nutrition in knee OA. Recent data highlight the detrimental effects of high-carbohydrate and high-fat diets, particularly those rich in refined sugars and saturated fats, which exacerbate systemic inflammation and contribute to cartilage degradation. Conversely, diets rich in omega-3 fatty acids, polyphenols, and dietary fiber have shown anti-inflammatory and chondroprotective properties. A Mediterranean diet rich in these nutrients effectively prevents the development of OA and its comorbidities, including obesity and cardiovascular disease. The role of supplements, such as glucosamine, chondroitin, and vitamin D, is questioned due to the lack of evidence supporting their efficacy in treating knee OA. Despite dietary recommendations published annually, there is still a need to debunk many myths that are not confirmed by current evidence. The significant research gaps require more extensive, controlled studies to establish evidence-based dietary recommendations (particularly carbohydrates, dietary fiber, and antioxidant intake). This comprehensive review provides insight into the various indications for the impact of nutrition on knee OA, focusing on key nutrients such as carbohydrates, fats, proteins, antioxidants, and selected micronutrients, providing the clinician with ready-to-implement nutritional modifications. Such an analysis may help clinicians and patients incorporate dietary strategies into treating knee OA, emphasizing the need for personalized, sustainable approaches. Full article

Osteoarthritis (OA), the most common degenerative pathology of the joints, affects mainly elderly people, and it is one of the most important factors causing disability. This study aimed to assess the effect of Juglans regia L. on rats with collagenase-induced knee osteoarthritis comparative with groups with the same disease treated with ellagic acid (EA), indomethacin as positive control and vehicle as negative control. After 2 and 4 weeks of treatment, blood samples were collected in order to evaluate the oxidative stress and inflammation, as well as RANKL and hydroxyproline levels. The results showed that EA improved the systemic antioxidant defense (p < 0.05), decreased the interleukin-6 (IL-6) secretion (p < 0 < 0.05) and RANKL levels (p < 0.01 and p < 0.001) at the same time enhancing hydroxyproline values, particularly after 2 weeks of treatment (p < 0.01). JR extract especially maintained low values of RANKL (p < 0.05) and hydroxyproline levels (p < 0.05), indicating a partial chondroprotective effect compared to EA. In conclusion, the use of EA and JR extract can improve some parameters of bone regeneration in experimental osteoarthritis, suggesting beneficial effects in articular inflammatory diseases. However, further studies are necessary to establish the optimum dose and time of treatment with both compounds in order to obtain optimal therapeutic results. Full article

Osteoarthritis (OA) remains a leading cause of disability worldwide, with no disease-modifying therapies currently available for treatment. The infrapatellar fat pad (IFP) harbors mesenchymal stem/stromal cells (MSC) with potent immunomodulatory and regenerative properties, making them a promising candidate for OA treatment. A growing body of evidence suggests that the therapeutic effects of MSC are largely mediated by their extracellular vesicles (EVs), which carry bioactive cargo that modulates inflammation and tissue repair. However, optimizing MSC-derived EVs as a cell-free therapeutic approach requires an in-depth understanding of how culture conditions and inflammatory/hormonal priming influence their functional properties. In this study, IFP-MSC were expanded in regulatory-compliant human platelet lysate (HPL) and xeno-/serum-free (XFSF) media and primed with an inflammatory/fibrotic cocktail (TIC) with oxytocin (OXT) to assess the impact on their immunophenotypic profile and EV cargo. The immunophenotype confirmed that TIC+OXT-primed MSC retained key immunomodulatory surface markers, while EV characterization verified the successful isolation of CD63+/CD9+ vesicles. Pathway enrichment analysis of both HPL- and XFSF- TIC+OXT EVs cargo identified key miRNAs associated with immune regulation, tissue repair, and anabolic signaling. Functional assays revealed that TIC+OXT EVs promoted M2-like anti-inflammatory macrophage polarization and exhibited chondroprotective properties in chondrocytes/synoviocytes inflammatory osteoarthritic assay. These findings highlight the therapeutic potential of TIC+OXT-primed IFP-MSC-derived EVs as immunomodulatory and chondroprotective agents, offering a promising strategy for OA treatment through a clinically viable, cell-free approach. Full article

Osteoarthritis (OA) is a chronically progressive degenerative arthropathy characterized by the loss of cartilage, changes in subchondral architecture, and ongoing inflammation resulting in reduced mobility and pain. This study assessed the treatment potential of a combination of chondroitin and glucosamine enriched with Curcumin C3 Complex (C3GC) in modulating the pathophysiological features in mouse models with surgically induced OA and in dogs with naturally occurring OA. A cohort of 24 male C57BL/6 mice aged 3 months old were surgically destabilized with medial meniscus (DMM) to cause osteoarthritis. These animals underwent a nutritional intervention with C3GC or with GC over a course of 8 weeks. In order to evaluate cartilage health and subchondral bone structure, we carried out a combination of behavioral tests, micro-computed tomography (micro-CT), and histopathological examinations. In addition, a cohort of 12 OA-diagnosed retired police dogs were administered C3GC supplements or conventional care over a course of 30 days, with pain measurement and serum concentrations of MMP-3 and TNF-α determined before and after treatment. According to our findings, the administration of C3GC was determined to preserve subchondral microarchitectural structure integrity (p < 0.05) and resulted in better motor function in comparison with GC. In animals taking nutritional supplements, the OARSI scores of joint tissue sections were reduced, with the medial tibial plateau OARSI score being particularly low in the C3GC group (p < 0.0001). In dogs, treatment with C3GC resulted in a 24.5% reduction in serum MMP-3 levels (p < 0.01), and there was also a 20.8% decrease in serum TNF-α levels (p < 0.05), along with a decrease in subjective pain assessment. The results are in support of the chondroprotective, anti-inflammatory, and analgesic properties of C3GC and justify future research on the potential utility of C3GC in treating osteoarthritis. Full article

Background: Osteoarthritis (OA) is a degenerative joint disease characterized by progressive cartilage breakdown, synovial inflammation, and pain, which leads to significant disability. IAHA is widely used because of its viscoelastic properties, which restore synovial fluid homeostasis and reduce symptoms. However, emerging evidence suggests that IAHA exerts additional biological effects including chondroprotection, inflammatory modulation, oxidative stress reduction, and pain modulation, which may influence disease progression. Objective: This narrative review examines the biological mechanisms underlying IAHA’s role in OA management. The review explored IAHA’s effects on synovial fluid viscoelasticity, inflammatory cytokine modulation, cartilage preservation, oxidative stress regulation, and pain pathways, emphasizing the influence of molecular weight variations on therapeutic efficacy. Additionally, this review evaluates IAHA’s integration into multimodal treatment strategies, its potential disease-modifying effects, and future directions for personalized treatment approaches. Methods: A comprehensive literature review was conducted using PubMed, Cochrane Library, EMBASE, Scopus, and Web of Science for studies published between January 2000 and March 2024. The search focused on IAHA’s molecular, cellular, and biochemical effects in OA and clinical findings assessing its impact on joint function, pain relief, and disease progression. Results: IAHA improves synovial fluid lubrication, reduces proinflammatory cytokines (IL-1β, TNF-α), inhibits matrix metalloproteinases (MMPs), scavenges reactive oxygen species (ROS), and modulates nociceptive pathways. High-molecular-weight IAHA demonstrates superior efficacy in advanced OA, while low-molecular-weight formulations may be better suited for early-stage disease. Although IAHA’s symptom relief is comparable to corticosteroids and NSAIDs, its favorable safety profile and emerging disease-modifying potential support its long-term use in OA management. Conclusions: IAHA represents a multifaceted therapeutic approach bridging symptomatic relief and regenerative strategies. While long-term efficacy, optimal administration protocols, and patient-specific responses remain subjects of ongoing research, refining treatment selection criteria, dosing regimens, and combination strategies may enhance clinical outcomes. Future studies should explore biomarker-driven approaches, standardize treatment protocols, and assess IAHA’s synergy with regenerative medicine to optimize its role in OA management. Full article

Osteoarthritis (OA) is a chronic and debilitating joint disease characterized by progressive cartilage degeneration for which no definitive cure exists. Conventional management approaches often rely on fragmented and poorly coordinated pharmacological and non-pharmacological interventions that are inconsistently applied throughout the disease course. Persistent controversies regarding the clinical efficacy of chondroprotective agents, frequently highlighted by pharmacovigilance agencies, underscore the need for a structured evidence-based approach. Emerging evidence suggests that synchronizing pharmacotherapy and exercise regimens with circadian biology may optimize therapeutic outcomes by addressing early pathological processes, including low-grade inflammation, oxidative stress, and matrix degradation. Recognizing the influence of the chondrocyte clock on these processes, this study proposes a ‘prototype’ for a novel framework that leverages the circadian rhythm-aligned administration of traditional chondroprotective agents along with tailored, accessible exercise protocols to mitigate cartilage breakdown and support joint function. In addition, this model-based framework emphasizes the interdependence between cartilage chronobiology and time-of-day-dependent responses to exercise, where strategically timed joint activity enhances nutrient and waste exchange, mitigates mitochondrial dysfunction, supports cellular metabolism, and promotes tissue maintenance, whereas nighttime rest promotes cartilage rehydration and repair. This time-sensitive, comprehensive approach aims to slow OA progression, reduce structural damage, and delay invasive procedures, particularly in weight-bearing joints such as the knee and hip. However, significant challenges remain, including inter-individual variability in circadian rhythms, a lack of reliable biomarkers for pharmacotherapeutic monitoring, and limited clinical evidence supporting chronoexercise protocols. Future large-scale, longitudinal trials are critical to evaluate the efficacy and scalability of this rational integrative strategy, paving the way for a new era in OA management. Full article

Inflammation plays a critical role in the pathogenesis of osteoarthritis (OA). The objective of this study was to investigate the anti-inflammatory and chondroprotective properties of Artemisia annua L. water extract (AWE) following the induction of inflammation in cartilage cells (SW1353 cell) through the administration of interleukin-1 beta (IL-1β). We demonstrated significant antioxidant activity, as evidenced by elevated total phenolic and flavonoid content, in addition to robust free radical scavenging capacity, as assessed through DPPH (2,2-diphenyl-1-picrylhydrazyl) and ABTS (2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) assays. Its cytotoxic effects were assessed at a concentration of 200 μg/mL, where no cytotoxic signs were observed in SW1353 cells treated with IL-1β; the levels of reactive oxygen species (ROS) were notably reduced in a dose-dependent manner. The principal inflammatory markers, cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS), were significantly diminished by AWE treatment. AWE administration led to a dose-dependent reduction in the expression of key proteins involved in the mitogen-activated protein kinase (MAPK) and nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) signaling pathways, ultimately resulting in a decrease in the release of matrix metalloproteinases (MMPs), specifically MMP-1 and MMP-13, which are known to contribute to cartilage degradation. Additionally, the levels of degraded collagen type II in the cartilage cells were restored. These findings suggest that reducing oxidative stress and inflammation, along with inhibiting activated MAPK and NF-κB signaling pathways, may ameliorate the progression of IL-1β-induced OA. Furthermore, a molecular docking analysis revealed a strong binding affinity of MMP-13, a critical mediator in the pathogenesis of OA. Six compounds were identified in AWE, corroborating its potential antioxidant and anti-inflammatory effects. Therefore, AWE may serve as a potentially useful therapeutic agent against OA by modulating inflammation-related mechanisms. Full article

Background/Objectives: The consumption of food rich in anthocyanins, a natural pigment found in plants, has been associated with improved joint health. However, systematic efforts to summarise the effects of anthocyanins and their deglycosylated forms, anthocyanidins, in managing osteoarthritis (OA) are lacking. This scoping review aims to comprehensively summarise the current evidence regarding the role of anthocyanins and anthocyanidins in OA management and highlights potential research areas. Methods: A comprehensive literature search was performed using PubMed, Scopus, and Web of Science in January 2025 to look for primary studies published in English, with the main objective of investigating the chondroprotective effects of anthocyanins and anthocyanidins, regardless of their study designs. Results: The seven included studies showed that anthocyanins and anthocyanidins suppressed the activation of inflammatory signalling, upregulated sirtuin-6 (cyanidin only), and autophagy (delphinidin only) in chondrocytes challenged with various stimuli (interleukin-1β, oxidative stress, or advanced glycation products). Anthocyanins also preserved cartilage integrity and increased the pain threshold in animal models of OA. No clinical trial was found in this field, suggesting a translation gap. Conclusions: In conclusion, anthocyanins and anthocyanidins are potential chondroprotective agents, but more investigations are required to overcome the gap in clinical translation. Full article

Osteoarthritis (OA), caused by the long-term use of joints, is a representative degenerative disease in the elderly. However, recently, the age of onset has been decreasing owing to excessive activities among young people in their 20s and 30s. Gynostemma pentaphyllum (Thunb.) Makino (GP), a perennial herb of the Cucurbitaceae family, has been used since the Ming dynasty as a medicinal material to treat various ailments, such as rheumatism, liver disease, and diabetes. In this study, we investigated the anti-arthritic effects of heat-processed Gynostemma pentaphyllum extract (Actiponin (AP)) and its derivatives, damulin A (DA) and damulin B (DB), using in vitro (primary rat chondrocytes and SW1353 cells) and in vivo (destabilization of the medial meniscus (DMM)-induced OA model) systems. Histological analysis results from the in vivo study showed that the group that underwent DMM surgery induced degeneration by the loss of proteoglycan and the destruction of cartilage (OARSI score 14 ± 0.57), whereas the group that received AP daily for 8 weeks maintained an intact condition (OARSI score 5 ± 0.28 at 200 mg/kg, p < 0.001). In addition, cartilage thickness and chondrocytes were reduced in the DMM group, but were restored in the AP-administered group. Furthermore, the von Frey analysis results showed that the pain threshold of the DMM group was considerably low (54.5 g at 8 weeks), whereas that of the AP group was dose-dependently increased (65.5, 69.5, 70.3, and 71.8 at 8 weeks for 30, 50, 100, and 200 mg/kg, respectively). In vitro studies showed that AP, DA, and DB reduced the expression of interleukin-1β alone-induced nitrite; inducible nitric oxide synthase; cyclooxygenase-2; matrix metallopeptidase 1/3/13; and a disintegrin and metalloproteinase with thrombospondin motifs 4/5. They also restored the expression of collagen type II and aggrecan, which are components of the extracellular matrix. The anti-arthritic effects of AP, DA, and DB were confirmed to be mediated by the mitogen-activated protein kinase and nuclear factor kappa-light-chain-enhancer of activated B cell signaling pathways. Collectively, these results suggest that AP is a potential therapeutic agent for mitigating OA progression and chondroprotection. Full article