Search Results (112)

Introduction: Osteoarthritis (OA), a leading cause of disability among the elderly, is characterized by progressive joint tissue destruction. Fucoidan, a sulfated polysaccharide with known anti-inflammatory and antioxidant properties, has been investigated for its potential to protect against interleukin-1 beta (IL-1β)-induced articular tissue damage. Methods: Human primary chondrocytes and synovial fibroblasts were pre-treated with 100 μg/mL fucoidan before stimulation with 1 ng/mL of IL-1β. The protective effects of fucoidan were assessed by measuring oxidative stress markers and catabolic enzyme levels. These in vitro findings were corroborated using a rat anterior cruciate ligament transection-induced OA model. To explore the underlying mechanisms, particularly the interaction between microRNAs (miRs) and heme oxygenase-1 (HO-1), five candidate miRs were identified in silico and experimentally validated. Luciferase reporter assays were used to confirm direct interactions. Results: Fucoidan exhibited protective effects against IL-1β-induced oxidative stress and catabolic processes in both chondrocytes and synovial fibroblasts, consistent with in vivo observations. Fucoidan treatment restored HO-1 expression while reducing inducible nitric oxide synthase and matrix metalloproteinase levels in IL-1β-stimulated cells. Notably, this study revealed that fucoidan modulates the miR-22/HO-1 pathway, a previously uncharacterized mechanism in OA. Specifically, miR-22 was upregulated by IL-1β and subsequently attenuated by fucoidan. Luciferase reporter assays confirmed a direct interaction between miR-22 and HO-1. Conclusion: The results demonstrate that fucoidan mitigates OA-related oxidative stress in chondrocytes and synovial fibroblasts through the novel modulation of the miR-22/HO-1 axis. The miR-22/HO-1 pathway represents a crucial therapeutic target for OA, and fucoidan may offer a promising therapeutic intervention. 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

Background: Proximal tibial fractures can lead to post-traumatic osteoarthritis (PTOA), and subsequent total knee arthroplasty (TKA) in such patients is associated with elevated complication rates. A two-stage approach, involving the elective removal of osteosynthetic hardware prior to TKA, is recommended. The utility of microbiological sampling from macroscopically unremarkable tissue during TKA implantation remains controversial. Objective: To retrospectively evaluate the rate of periprosthetic joint infection (PJI) following TKA after PTOA and to assess the potential benefit of intraoperative microbiological sampling. The secondary objective was to evaluate the presence of prior colonization in osteosynthetic hardware among the affected cases. Patients and Methods: A retrospective screening of the hospital database was conducted between 2008 and 2022, including only AO/OTA type 41-B and 41-C fractures. Patients were assigned to a sampling group (with microbiological sampling during TKA) or a control group (without sampling). All patients received structured follow-up to assess postoperative complications. Results: A total of 40 patients met the screening criteria. In the sampling group (n = 29), 17.24% required surgical revision, and the rate of PJI was 3.45%. In the control group (n = 11), 18.14% underwent revision surgery, with a PJI rate of 9.09%. The average follow-up period was 4.35 years (range 2–11.6 years). Discussion: TKA in patients with PTOA is associated with a heightened risk of complications. A noteworthy possible correlation between systematic microbiological sampling and reduced PJI incidence was observed. While the small sample size limits definitive conclusions regarding causality, the findings support the potential value of consistent intraoperative sampling. 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

Osteoarthritis (OA) is a prevalent and debilitating joint disease in older adults with a complex etiology. We investigated the role of SUMOylation, a post-translational modification, in OA pathogenesis, focusing on the mitochondrial chaperone Prohibitin (PHB1) and the cartilage homeostasis transcription factor PITX1. We hypothesized that oxidative stress-induced SUMOylation promotes PHB1 nuclear accumulation, leading to PITX1 downregulation and contributing to OA development. Analysis of cartilage specimens from 27 OA patients and 4 healthy controls revealed an increased nuclear accumulation of PHB1 in OA chondrocytes, accompanied by elevated levels of SUMO-1 and SUMO-2/3. Mechanistically, nuclear PHB1 interacted indirectly with SUMO-1 through a SUMO-interacting motif (SIM), and the deletion of this SIM prevented PHB1 nuclear trapping in OA cells. Furthermore, the SUMO-conjugating enzyme E2 (UBC9) encoded by the UBE2I gene was upregulated in knee OA cartilage, and its overexpression in vitro enhanced PHB1 nuclear accumulation. Consistently, transgenic mice overexpressing the Ube2i gene exhibited increased UBC9 in their knee cartilage, resulting in Pitx1 downregulation and the emergence of an early OA-like phenotype in articular chondrocytes. Our findings uncover a novel role for UBC9-mediated SUMOylation in primary knee and hip OA. This pathway enhances PHB1 nuclear accumulation, contributing to PITX1 repression and subsequent OA development. These results underscore the importance of SUMOylation in OA pathogenesis and suggest potential molecular targets for early diagnosis and therapeutic intervention. Full article

Background: Diacerein, a prodrug of Rhein, is commonly prescribed for the management of joint disorders, specifically osteoarthritis. This study aimed to develop and validate an LC-MS/MS method to quantify Rhein and its major metabolites, Rhein-G1 and Rhein-G2, in plasma samples. Method: An ACE C18 column was used for chromatographic separation with a mobile phase comprising ammonium acetate at a concentration of 1.0 mM and acetonitrile. Detection was achieved using a Sciex 4000 Q-Trap LC-MS/MS, operated in negative ion mode with multiple reaction monitoring (MRM). Results: The analytical results indicated that the lower limit of quantification (LLOQ) for Rhein and its glucuronides was 7.81 nM. Precision was consistently below 9.14%, while accuracy remained within the acceptable range of 80.1–104.2%. We also verified the method’s matrix effect recovery and stability variance, which were less than 12.60% and 10.37%, respectively. The pharmacokinetic study demonstrated that diacerein is swiftly metabolized into Rhein, and then Rhein subsequently undergoes glucuronidation, forming detectable concentrations of Rhein-G1 and Rhein-G2 in plasma. Conclusions: This new LC-MS/MS method proved to be both sensitive and selective, allowing for pharmacokinetic studies in rats. Full article

There is limited information about the orthopaedic health of dressage horses. This study aimed to document the orthopaedic status, lesion distribution, and evolution of injuries in 70 horses undergoing a minimum of five in-depth orthopaedic assessments at six-months’ intervals. Warmblood (70.0%) and Iberian (24.3%) breeds predominated. The median lameness grade at initial examination was 2/5 (interquartile range 2,2; range 0,3). Hypermetria (42.9%) or hypermetria and weakness (12.9%) were observed at the initial examination and did not change over time. Metacarpophalangeal/metatarsophalangeal joint region injuries (osteoarthritis or suspensory branch injury), 58.6%, predominated at the initial examination; there was a high proportion of persistent or recurrent injuries (90%). Metacarpal/metatarsal region pain (predominantly suspensory desmitis) had a high prevalence at all examinations (24.3–41.4%), and a high proportion of recurrent injury (90%). There was an increase in spinal pain comparing the initial and final examinations (McNemar’s p < 0.001); 21.4% of horses with thoracic region pain subsequently developed lumbosacroiliac region pain. Twenty-six (37.1%) increased work level; nineteen (27.1%) remained at the same level, with 37% competing at Intermediate I or II, under 25 international, or Grand Prix at the final examination, compared with 3% at the initial examination. Serial monitoring and targeted treatment may facilitate horses reaching athletic potential. 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

Introduction: The present study investigates the five-year outcomes of hip arthroscopy for cam or pincer-type femoroacetabular impingement (FAI) and associated labral tears in a defined patient population. Methods: Patients who underwent hip arthroscopy for cam or pincer-type arthroscopy femoroacetabular impingement (FAI) and labral tears at our hospital in the past five years were included. All patients who underwent revision—like a total hip arthroplasty (THA), a subsequent hip arthroscopy at another hospital, or had primary osseous diseases—were excluded. Patients were contacted via mail and asked to answer a clinical questionnaire called the “Hip Osteoarthritis Outcome Score” (HOOS) and to indicate whether there was a second surgery like a subsequent arthroscopy or THA. Results: There were 77 hip arthroscopies in 75 patients the last 5 years. A total of 29 patients responded. Those who did not respond were contacted via phone. All in all, we obtained the results of 49 patients (50 hips—29 right, 19 left, and 1 bilateral) who underwent hip arthroscopy over the past five years. The mean age at the time of operation was 41 years. Our results were as follows: 24 hips had an isolated labral tear, 49 hips a combined FAI pathology with cam and/or pincer-type impingement and labral tears, 3 patients had a posttraumatic FAI, and 1 patient suffered from hip chondromatosis, who was subsequently excluded; further, 22 patients (23 procedures) were lost to follow-up. HOOS contains various subscales; only the postoperative result of subscale 1 (symptoms) did not show a statistically significant improvement compared with the preoperative value. All other subscales showed a statistically significant improvement in comparison with the preoperative condition. Five patients (10.2%) still experienced symptoms, so we performed a total hip arthroplasty (THA) as a second surgical procedure. One patient was revised due to chondromatosis. One patient was revised at another center, and another was excluded because of chondromatosis. Conclusions: The five-year follow-up results of hip arthroscopy proved successful outcomes. Hip arthroscopy is an effective treatment for FAI in order to delay primary THA, regaining mobility and range of motion and reducing pain. Longer-term studies with a larger cohort are necessary. Full article

The specific pathogenesis of osteoarthritis (OA) remains not fully understood. As a transmembrane heparan sulfate proteoglycan, syndecan-4 (SDC4) has been proven to play an important role in the development of OA. Notably, the extracellular domain of SDC4 can be cleaved by proteolytic enzymes, leading to the release of shed SDC4 (sSDC4), which subsequently regulates various biological processes in an autocrine or paracrine manner. This review analyzed 97 publications (1987–2025) from Pubmed and the Web of Science Core Collection using specific key words (syndecan-4, shed syndecan-4, and osteoarthritis), providing a comprehensive overview of the current research on sSDC4, including its shedding enzymes and specific cleavage sites, as well as the factors and mechanisms that influence SDC4 shedding. Furthermore, it summarizes the functions of both sSDC4 and its remaining membrane-bound domain. Finally, the roles of sSDC4 in OA are discussed to identify potential therapeutic targets and explore new strategies for the treatment of OA. Full article

Omega-3 polyunsaturated fatty acids (n-3 PUFAs) are known to help resolve inflammation through generation of anti-inflammatory eicosanoids and specialized pro-resolving mediators, including resolvins, protectins, and maresins. Through binding to the GPR120/FFAR4 receptor, their beneficial effects result from phospholipid membrane remodeling, impairment of inflammatory signaling molecules clustering, subsequent inhibition of NF-κB and inflammasome activation, and a reduction in oxidative stress. Obesity, a chronic inflammatory disease that contributes to metabolic disorders, is alleviated by n-3 PUFAs. In the adipose tissue (AT) of individuals with obesity, n-3 PUFAs counteract hypoxia, inhibit immune cell infiltration and AT inflammation, improve insulin sensitivity, and reduce fat mass. Beyond AT, n-3 PUFAs also alleviate other metabolic disorders such as metabolic-associated steatotic liver disease (MASLD), gut dysbiosis, and/or renal dysfunction. In cardiovascular disease (CVD), they are mainly recommended as a secondary prevention for patients with coronary heart disease risks. This review provides an in-depth analysis of the benefits of n-3 PUFAs in obesity and related metabolic diseases, examining both the mechanistic and clinical aspects. Additionally, it also explores the effects of n-3 PUFAs in obesity-related chronic inflammatory conditions, including inflammatory bowel disease, psoriasis, rheumatoid arthritis, osteoarthritis, and multiple sclerosis, by targeting specific pathophysiological mechanisms. Clinical applications and limitations of n-3 PUFAs are discussed based on findings from human clinical trials. Full article

Post-traumatic osteoarthritis (PTOA) is a common cause of lameness in the horse. There is no cure, therefore treatments are aimed at reducing pain and improving the joint environment by modifying inflammatory pathways or by viscosupplementation. Here, we report the safety and efficacy of the biolubricant (poly(2-methacryloyloxyethyl phosphorylcholine; pMPC) to mitigate the physical, gross, histological, and biochemical effects of arthritis. We created an osteochondral fragment in the middle carpal joint of one limb in 16 horses to induce PTOA; the contralateral limb served as a sham-operated joint. Two weeks postoperative, half (n = 8) of the horses received a single injection of pMPC in the PTOA joint, while the other half received saline. All sham-operated joints (n = 16) received saline. We conducted clinical evaluations weekly while synovial fluid biomarkers were measured biweekly during the 70-day study period. Subsequently, we performed postmortem gross and histologic analyses. Horses in which PTOA joints were treated with pMPC exhibited mild increases in clinical data, including lameness, effusion, and flexion scores. Similarly, synovial cell count, total protein, and prostaglandin E₂ values were higher for pMPC-treated joints. Radiographic changes included significantly higher osteophyte scores in pMPC-treated joints at the terminal timepoint. The biolubricant may demonstrate some chondroprotective effects with lower total erosion scores and higher cartilage glycosaminoglycan content. In summary, when pMPC is administered to PTOA joints, the biolubricant induces a mild inflammatory response but may offer some chondroprotective effects in horses. Full article

Background: The aim of this study was to evaluate the balance in extension and flexion achievable after total knee arthroplasty (TKA) using a modified kinematic alignment (KA) plan and the subsequent balance achievable after adjusting the component based on the functional alignment (FA) principle. Methods: This retrospective cohort study included 100 consecutive patients who underwent primary TKA for knee osteoarthritis through an image-based robotic system in a single center between October 2021 and February 2022. Whether modified KA or FA could achieve a balanced knee was evaluated by assessing the ligament balance in the medial and lateral compartments using a robotic system at extension and 90° flexion. Balance was defined as a difference of ≤2 mm between the compartments. Component positioning was adjusted within limits based on the functional positioning principles to achieve balance. Implant positioning and balance in extension and 90° flexion were compared between the modified KA plan (n = 100) and after FA adjustments (n = 100). Results: FA achieved significantly better balance in extension (FA, 99.0% vs. modified KA, 86.0%; p = 0.001) and flexion (98.0% vs. 43.0%; p < 0.001) than the modified KA plan. The mean difference in gap balance in extension (FA, 0.1 mm vs. modified KA, 0.6 mm; p = 0.001) and flexion (0.1 mm vs. 2.3 mm; p < 0.001) was also significant between the two techniques. The femoral component was positioned more externally rotated relative to the transepicondylar axis (FA, 2.5° vs. modified KA, 0.0°; p < 0.001) to obtain balanced targets. There were significant improvements in the patient-reported outcome measures between preoperative and postoperative assessments two years after TKA (all p < 0.05). Conclusions: FA consistently achieved superior balance in both extension and flexion following TKA compared with modified KA without altering the soft tissue envelope, leading to significant improvements in clinical outcomes at the two-year follow-up. Full article

Background: Knee osteoarthritis (OA) is a prevalent degenerative joint disease characterized by the degeneration of joint cartilage. Knee OA leads to pain, stiffness, swelling, and decreased mobility, significantly impacting the quality of life of affected people. Advanced-stage osteoarthritis often necessitates surgical intervention due to poor response to conventional treatments, such as intra-articular hyaluronic acid (HA). Carboxymethyl-chitosan (CM-C), an emerging therapeutic agent, has shown potential in reducing inflammation, improving lubrication, and enhancing joint function. This study aimed to evaluate the long-term efficacy of CM-C injections in patients with advanced knee osteoarthritis, non-responders to HA. Methods: This retrospective study included 16 patients (mean age: 79.56 years) with Kellgren–Lawrence grade 3–4 knee OA treated with a single intra-articular injection of CM-C. Pain and functional outcomes were assessed using the Visual Analogue Scale (VAS) and Knee Injury and Osteoarthritis Outcome Score (KOOS) at baseline (T0), one month (T1), three months (T2), six months (T3), and twelve months (T4). Results: Significant pain reduction was observed at early follow up, (VAS: T1 p = 0.0002, T2 p = 0.0265; KOOS Pain: T1 p = 0.0014). However, pain partially returned by T3 and T4. KOOS activities of daily living (p = 0.0005), QoL (p = 0.0396), and Sport and Free Time (p = 0.0367) subscales showed significant improvement at T1, though worsening trends were observed in subsequent follow up with raw values suggesting persistent benefits. Strong negative correlations were found between VAS and KOOS subscales at various follow ups. Conclusions: A single CM-C injection demonstrated early pain relief and functional improvement in advanced knee OA for non-responders to HA. However, the long-term effects may diminish over time, necessitating a careful consideration of re-treatment strategies or combined therapies. Full article

Background: Knee osteoarthritis is a prevalent condition that significantly impacts patients’ quality of life. Effective management typically involves a combination of pharmacological and non-pharmacological treatments. However, establishing a consensus on the optimal treatment strategy is crucial for standardizing care. The present study is the result of a rigorous process that combines artificial intelligence with human expertise to improve the reliability of medical recommendations. Methods: A new software platform (Butterfly Decisions, 2021, Italy) was employed to leverage AI-assisted decision-making, facilitating the digitalization of the entire consensus process. The process started with data collection through an online survey including simulated clinical cases of knee osteoarthritis collected by 30 orthopedic surgeons; artificial intelligence (AI) analyzed the collected clinical data and identified the key concepts and relevant patterns. Subsequently, AI generated detailed statements summarizing key concepts extracted from the data and proposed a reformulation of the statements to be discussed during the discussion session of the advisory board. The advisory board, composed of four qualified, experienced specialists of knee osteoarthritis, evaluated statements, providing their agreement levels, confidence, and supporting evidence. The AI tools calculated the degree of certainty and contradiction for each statement based on these evaluations. The literature was critically evaluated to ensure that there was an evidence-based evaluation of the proposed treatment statements. Finally, revised versions were proposed to address the feedback, evidence was collected to refine the scientific report, and the board members evaluated the AI performance too. Results: The consensus analysis revealed a high level of agreement in the need for a multimodal approach to treating knee osteoarthritis. The feedback highlighted the importance of integrating physical therapy and weight management, non-pharmacological methods, with Symptomatic Slow-Acting Drug for Osteoarthritis (SYSADOAs) and pharmacological treatments, such as anti-inflammatory drugs and intra-articular knee injections. The board members found that AI was easy to use and understand and each statement was structured clearly and concisely. Conclusions: The expert consensus about knee osteoarthritis conservative management being facilitated with AI met with unanimous agreement. AI-assisted decision-making was shown to have excellent analytical capabilities, but algorithms needs to be trained by orthopaedic experts with the correct inputs. Future additional efforts are still required to evaluate the incorporation of AI in clinical workflows. Full article