Search Results (1,118)

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: Septic arthritis is an orthopedic emergency. However, optimal biomarkers and diagnostic criteria remain unclear. The study aimed to evaluate the diagnostic performance of routinely used and novel biomarkers, including serum C-reactive protein (CRP), synovial white blood cells (WBC), pentraxin-3 (PTX3), interleukin-6 (IL-6), and presepsin, in distinguishing septic from non-septic arthritis. Methods: Thirty-one patients undergoing arthrocentesis were included. Patients were categorized into septic and non-septic arthritis groups. Synovial fluid and serum samples were analyzed for five biomarkers. Diagnostic performance was assessed by calculating the area under the curve (AUC), accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Results: Synovial WBC demonstrated the highest diagnostic performance among single biomarkers (AUC = 0.837, p = 0.012). Among novel biomarkers, PTX3 showed the highest accuracy and sensitivity. The serum CRP and synovial WBC combination yielded an AUC of 0.853, with 100% sensitivity, 68.0% specificity, 42.9% PPV, and 100% NPV. Adding all three novel biomarkers to this combination increased the AUC to 0.887 (p = 0.004), maintaining 100% sensitivity and NPV. When individually added, PTX3 achieved 100% sensitivity and NPV, while presepsin showed the highest specificity (96.0%), PPV (75.0%), and accuracy (87.1%). Conclusions: Serum CRP and synovial WBC remain essential biomarkers for diagnosing septic arthritis; however, combining them with PTX3, IL-6, and presepsin improved diagnostic accuracy. PTX3 is best suited for ruling out septic arthritis due to its high sensitivity and NPV, whereas presepsin is more useful for confirmation, given its specificity and PPV. These results support a tailored biomarker approach aligned with diagnostic intent. Full article

Inflammatory arthritis (IA) is a chronic condition marked by joint dysfunction and pain, posing significant challenges for effective drug delivery. This study separated Perilla frutescens leaf-derived exosome-like nanovesicles (PFE) to effectively penetrate the stratum corneum barrier. These nanovesicles and indomethacin (IND) were subsequently developed into a nanogel designed for topical drug delivery systems (PFE-IND-GEL). PFE exhibited a typical vesicular structure with a mean diameter of 98.4 ± 1.3 nm. The hydrodynamic size and zeta potential of PFE-IND-GEL were 129.6 ± 5.9 nm and −17.4 ± 1.9 mV, respectively. Mechanistic investigations in HaCaT keratinocytes showed that PFE significantly downregulated tight junction proteins (ZO-1 and Occludin, p < 0.01) via modulation of the IL-17 signaling pathway, as evidenced by transcriptomic analysis. In a sodium urea crystal-induced rat IA model, the topical application of PFE-IND-GEL significantly reduced joint swelling (p < 0.05) and serum levels of inflammatory cytokines (IL-6, IL-1α, TNF-α) compared to control groups. Histopathological analysis confirmed the marked attenuation of synovial inflammation and cartilage preservation in treated animals. These findings underscore the dual role of PFE as both a topical permeation enhancer and an anti-inflammatory agent, presenting a promising strategy for managing IA. Full article

Background: Rheumatoid arthritis (RA) is an autoimmune disease that remains incurable. An increasing number of proteomic genome-wide association studies (GWASs) are emerging, offering immense potential for identifying novel therapeutic targets for diseases. This study aims to identify potential therapeutic targets for RA based on human plasma proteome. Methods: Protein quantitative trait loci were extracted and integrated from eight large-scale proteomic GWASs. Proteome-wide Mendelian randomization (Pro-MR) was performed to prioritize proteins causally associated with RA. Further validation of the reliability and stratification of prioritized proteins was performed using MR meta-analysis, colocalization, and transcriptome-wide summary-data-based MR. Subsequently, prioritized proteins were characterized through protein–protein interaction and enrichment analyses, pleiotropy assessment, genetically engineered mouse models, cell-type-specific expression analysis, and druggability evaluation. Phenotypic expansion analyses were also conducted to explore the effects of the prioritized proteins on phenotypes such as endocrine disorders, cardiovascular diseases, and other immune-related diseases. Results: Pro-MR prioritized 32 unique proteins associated with RA risk. After validation, prioritized proteins were stratified into four reliability tiers. Prioritized proteins showed interactions with established RA drug targets and were enriched in an immune-related functional profile. Four trans-associated proteins exhibited vertical or horizontal pleiotropy with specific genes or proteins. Genetically engineered mouse models for 18 prioritized protein-coding genes displayed abnormal immune phenotypes. Single-cell RNA sequencing data were used to validate the enriched expression of several prioritized proteins in specific synovial cell types. Nine prioritized proteins were identified as targets of existing drugs in clinical trials or were already approved. Further phenome-wide MR and mediation analyses revealed the effects and potential mediating roles of some prioritized proteins on other phenotypes. Conclusions: This study identified 32 plasma proteins as potential therapeutic targets for RA, expanding the prospects for drug discovery and deepening insights into RA pathogenesis. Full article

Background/Objectives: The rising demand for total joint arthroplasty (TJA) and increasing incidence of prosthetic joint infections (PJIs) significantly burden patients and healthcare systems. This retrospective study describes the epidemiology, clinical characteristics and outcomes of PJIs in Iceland from 2003 to 2020. Methods: PJI cases were identified through synovial fluid cultures and ICD codes, with classification per EBJIS criteria. Unlikely cases were excluded. Results: Among 293 cases with a mean age of 70 years, 60% (176/293) were males and 58% (171/293) involved the knee. Over half of infections occurred within two years post TJA, with an incidence rate of 0.94%, increasing significantly over time (p = 0.012). Males had significantly higher incidence rates than females (incidence rate ratio 0.42; p < 0.001). The most common pathogens were coagulase-negative staphylococci (30%, 88/293), and 9% (27/293) of cases were culture-negative. DAIR was the first-line treatment in about 50% (147/293) of cases but it failed in nearly half, contributing to an overall treatment failure rate of 38% (98/259). PJI-related mortality was 2% (6/293). Conclusions: The results indicate an increased incidence, with the highest risk within two years of TJA. Males are at greater risk, while females more commonly undergo TJA. DAIR success rates were lower than reported elsewhere but improved significantly over time. Better methods to prevent PJIs are needed. Full article

Obesity, characterized by excessive or abnormal accumulation of body fat, is associated with a range of metabolic and inflammatory diseases, including osteoarthritis (OA). In obese individuals, adipose tissue expansion—via adipocyte hypertrophy or hyperplasia—is accompanied by altered secretion of adipokines such as leptin and adiponectin, which play significant roles in immune modulation, metabolism, and skeletal homeostasis. Leptin, acting through the hypothalamus, regulates the sympathetic nervous system and modulates hormonal axes, influencing bone metabolism and cartilage integrity. Elevated leptin concentrations in the synovial fluid, and the presence of its receptors on cartilage surfaces, suggest its direct role in cartilage degradation and OA progression. Conversely, adiponectin exerts anti-inflammatory effects, modulates osteoblast and macrophage activity, and appears to have a protective function in joint metabolism. These findings underscore the complex interplay between the adipose tissue, adipokines, and the osteochondral unit, highlighting the importance of their balance in maintaining joint health. Full article

Introduction/Objectives: Osteoarthritis (OA) is a chronic systemic disease that affects the entire array of joint structures. It is one of the most common chronic, socially significant diseases, associated with a decline in the quality of life of patients and constantly increasing the cost of treatment. Clinical trial outcomes are largely inconclusive, and OA remains one of the few musculoskeletal diseases without an established disease-modifying therapy. One potential explanation is the use of ineffective tools for OA classification, patient stratification, and the assessment of disease progression. There is growing interest in musculoskeletal ultrasonography (MSK US), as it enables the dynamic visualization of the examined structures and gives information about both inflammatory and structural changes that have occurred. Determining the leading ultrasound phenotype, which depends on the most damaged tissue at a given time (bone, cartilage, synovial membrane, joint capsule, ligaments, tendons, menisci, etc.), can rationalize therapy use by selecting patients more suitable for specific treatments. This article aims to evaluate and summarize the potential of MSK US in the process of determining the clinical phenotype of OA and to emphasize the importance of this imaging modality in evaluating further therapeutic strategies. Method: A single-center prospective study conducted in the period of September 2023–June 2024 enrolled 259 consecutive patients with proven OA. The statistical program Minitab version 22.2.1 (2025) was used to analyze the data. The predominant and secondary phenotypes were tabulated for each OA localization and were presented numerically and as relative proportions (%). The rate of the most frequently occurring phenotypes was compared against that of the less frequent ones through paired z-tests. The initially acceptable type I error was set at 5%; it was further adjusted for the number of comparisons (Bonferroni). Results: The most frequent and predominant US phenotype for patients with knee OA was intra-articular effusion (n = 47, 37.90%). It was significantly higher compared to the rest of the US phenotypes: synovial proliferation (n = 22, 17.70%; p < 0.001), cartilage destruction (n = 26, 21%; p = 0.001), altered subchondral bone (n = 8, 6.50%; p < 0.001), extra-articular soft tissue changes (n = 12, 9.70%; p < 0.001), crystal deposits (n = 6, 4.8%; p < 0.001), and post-traumatic (n = 3, 2.40%; p < 0.001). The most common US phenotype for hip OA was altered subchondral bone (n = 32, 47.1%), with significant differences from intra-articular effusion (n = 12, 17.60%; p = 0.001), synovial proliferation (n = 5, 7.40; p = 0.001), cartilage destruction (n = 12, 17.60%; p = 0.001), extra-articular soft tissue changes (n = 3, 4.40%; p = 0.001), crystal deposits (n = 3, 4.40%; p = 0.001), and post-traumatic (n = 0). Altered subchondral bone was also the leading US phenotype for hand OA (n = 31, 55.40%), with significant differences compared to intra-articular effusion (n = 1, 1.80%; p < 0.001), synovial proliferation (n = 7, 12.50%; p < 0.001), cartilage destruction (n = 11, 19.60%; p < 0.001), extra-articular soft tissue changes (n = 2, 3.60%; p < 0.001), crystal deposits (n = 3, 5.40%; p < 0.001), and post-traumatic (n = 1, 1.80%, p < 0.001). For shoulder OA, extra-articular soft tissue changes were the most frequent (n = 8, 46.20%), followed by post-traumatic (n = 4, 30.70%), as the rate of both phenotypes was significantly higher compared to that of intra-articular effusion (n = 0), synovial proliferation (n = 0), cartilage destruction (n = 1, 7.70%; p = 0.003), and crystal deposits (n = 0). Conclusions: The therapeutic approach for OA is a dynamic and intricate process, for which the type of affected joint and the underlying pathogenetic mechanism at a specific stage of the disease’s evolution is essential. MSK US is one of the options for the clinical phenotyping of OA. Some of the suggested ultrasound subtypes may serve as the rationale for selecting a particular treatment. Full article

Sarcomas are heterogeneous mesenchymal tumors, and their pharmacological treatment remains challenging due to the high toxicity and poor efficacy of current therapies. This study aimed to identify common overexpressed kinases in the four most frequent sarcoma subtypes to establish novel therapeutic targets. A bioinformatics approach using patient-derived gene expression data sets identified overexpressed kinases shared across these sarcoma types. Later, BUB1 was determined as the kinase consistently overexpressed across the osteosarcoma, liposarcoma, leiomyosarcoma, and synovial sarcoma. Moreover, the role of this kinase was further validated through molecular and functional assays, including pharmacological inhibition in cell lines derived from the four sarcoma subtypes. BUB1 inhibition reduced the phosphorylation of AKT and H2A proteins, precluded cell proliferation, and inhibited colony formation in sarcoma cells. Finally, overall survival analysis highlighted a strong correlation between high BUB1 expression and poorer survival rates in sarcoma patients. Altogether, these findings underscore the potential of BUB1 as a therapeutic target and prognostic marker in sarcomas. Targeted inhibition of BUB1 may provide a novel strategy to reduce tumor growth and improve outcomes for patients with bone and soft tissue sarcomas. Full article

Rheumatoid arthritis (RA) is a progressive and systemic autoimmune disease, characterized by a chronic inflammatory process, affecting the lining of the synovial joints, many body organs/systems, and blood vessels. Its pathological hallmarks are hyperplasic synovium, bone erosion, and progressive joint destruction. Rheumatoid arthritis affects over 20 million people, with a worldwide prevalence of 0.5–1.0%, exhibiting gender, ethnic, and geographical differences. The progressive disability severely impairs physical motion and quality of life and is finally leading to a shortened life span. The pathogenesis of RA is a complex and still poorly understood process in which genetic and environmental factors are principally associated. Current treatment mostly relies on conventional/non-biological disease-modifying anti-rheumatic drugs (cDMARDs), analgesics, non-steroidal anti-inflammatory drugs, glucocorticoids, steroids, immunosuppresants, and biologic DMARDs, which only control inflammation and pain. Along with side effects (drug toxicity and intolerance), these anti-rheumatic drugs possess limited efficacy. Therefore, the discovery of novel multi-target therapeutics with an improved safety profile that function as inhibitors of RA-linked signaling systems are in high demand, and this is in the interest of both patients and clinicians. Plant-derived extracts, nutritional supplements, dietary medicine, and molecules with anti-inflammatory activity represent promising adjuvant agents or alternatives for RA therapeutics. This review not only aims to discuss the basic features of RA pathogenesis, risk factors, and signaling pathways but also highlights the research progress in pre-clinical RA in in vitro and in vivo models, revealing new avenues in the management of the disease in terms of comprehensive multidisciplinary strategies originating from medicinal plants and plant-derived molecules. Full article

Background: Immune checkpoint inhibitors (ICIs) transformed cancer treatment, producing significant survival benefits. However, ICIs can trigger toxicities called immune-related adverse events (irAEs), including inflammatory arthritis (IA) and polymyalgia rheumatica (PMR)-like syndromes. Our study aimed to systematically further characterize musculoskeletal ultrasound (MSKUS) findings in patients with ICI-IA and ICI-PMR, collectively referred to as “MSK-irAEs”, and explore the role of US in guiding treatment. Methods: The authors conducted a comprehensive chart review for patients receiving ICIs undergoing MSKUS at our center’s rheumatology clinics. US examinations were performed and reviewed by two MSKUS-certified rheumatologists. Descriptive statistics were performed to summarize demographic, clinical, and treatment-related variables. US findings were categorized with a novel scoring system: 0—no signs of inflammatory arthropathy or tendinopathy, 1—potential signs of inflammation (grayscale ≥ 2, effusion without power Doppler, synovial hypertrophy in the joint), and 2—active inflammation in joints and/or tendons (characterized by power Doppler) and signs of inflammation. Results: Twenty-three patients were included. The median age was 63 years, 52% were male, and 87% were White. Melanoma was the most common cancer (48%). MSK-irAEs were diagnosed in nineteen (83%), with MSKUS showing inflammation in seventeen (74%). Sixteen (70%) received escalation in MSK-irAE treatment after MSKUS. Four (17%) had erosive disease due to MSK-irAEs, while one had erosive osteoarthritis. Individuals with inflammatory erosive changes experienced prolonged intervals between symptom onset and MSKUS, ranging from 17 to 82 months, suggesting that erosions may reflect chronic, under-recognized inflammation. On MSK-irAE therapy, nine (47%) experienced symptomatic improvement, five (26%) achieved resolution, and in four (21%) cases, it was too early to assess the response. MSKUS detected other causes of MSK symptoms besides MSK-irAEs in several patients, allowing ICI resumption in one. Conclusions: Our study highlights the clinical utility of MSKUS not only as a diagnostic tool but also to guide therapeutic decision-making. Full article

Rheumatoid arthritis (RA) is one of the most representative autoimmune diseases. The peculiarity of this disease is synovial inflammation, which results in joint destruction and often disability. Although there are still several pathogenetic mechanisms to be clarified, lately, most studies have highlighted the involvement of mitochondria in the onset and progression of the disease. Mitochondrial functions are connected to many metabolic processes and the delivery of proinflammatory mediators. Mitochondria play a crucial role in the physiopathology of RA, contributing to chronic inflammation, cartilage and bone injury and chronic autoimmune response. Mitochondrial activity influences many aspects of the disease that will be discussed in terms of their correlation with the onset and persistence of RA, starting from mitochondrial dynamics up to bone homeostasis, passing through DAMPs and affecting immune cell functionality. Recent therapeutic approaches aim to improve mitochondrial function, reduce oxidative stress, modulate mitochondria-mediated inflammation and restore energy metabolism homeostasis. Full article

Background/Objectives: The aim of this study was to compare the clinical outcomes of cyst excision alone and the combination of excision and unilateral dynamic instrumentation in the surgical treatment of lumbar synovial cysts at the L4–L5 level and to determine which surgical approach is more effective. Methods: Thirty-three patients who underwent operations on the L4–L5-level synovial cyst in a single center between January 2015 and January 2021 were included in this retrospective study. Patients were divided into two groups: cyst excision only (n = 18) and excision with unilateral dynamic instrumentation (n = 15). The pain levels of the patients were assessed by VAS score, and their functional status was assessed by the Oswestry Disability Index. The mean follow-up period was 28.2 ± 4.0 months in the excision group and 27.6 ± 4.4 months in the instrumentation group. Results: VAS and ODI scores improved significantly in both groups (p < 0.001). The improvement in low back pain VAS scores was more significant in the instrumentation group (delta VAS: −5.8 ± 1.3 vs. −5.0 ± 1.2, p = 0.042). The complication rate was 27.8% in the excision group and 13.3% in the instrumentation group. The development of listhesis was significantly more frequent in the excision group (16.7% vs. 0%, p = 0.028). Reoperation rates were 16.7% in the excision group and 6.7% in the instrumentation group. Conclusion: Although both surgical approaches are effective in the treatment of synovial cysts at the L4–L5 level, the addition of dynamic instrumentation unilaterally seems to be more advantageous, especially in the control of low back pain and prevention of listhesis risk. The choice of surgical technique should be individualized by considering patient-specific factors. Full article

Current osteoarthritis (OA) therapies fail to yield long-term clinical benefits, due in part to the lack of a mechanism for the targeted and confined delivery of therapeutics to OA joints. This study evaluates if M2 macrophages are effective cell vehicles for the targeted and confined delivery of therapeutic genes to OA joints. CT bioluminescence in vivo cell tracing and fluorescent microscopy reveal that intraarticularly injected M2 macrophages were recruited to and retained at inflamed synovia. The feasibility of an M2 macrophage-based adoptive gene transfer strategy for OA was assessed using IL-1Ra as the therapeutic gene in a mouse tibial plateau injury model. Mouse M2 macrophages were transduced with lentiviral vectors expressing IL-1Ra or GFP. The transduced macrophages were intraarticularly injected into injured joints at 7 days post-injury and OA progression was monitored with plasma COMP and histology at 4 weeks. The IL-1Ra-expressing M2 macrophage treatment reduced plasma COMP, increased the area and width of the articular cartilage layer, decreased synovium thickness, and reduced the OARSI OA score without affecting the osteophyte maturity and meniscus scores when compared to the GFP-expressing M2 macrophage-treated or PBS-treated controls. When the treatment was given at 5 weeks post-injury, at which time OA should have developed, the IL-1Ra-M2 macrophage treatment also reduced plasma COMP, had a greater articular cartilage area and width, decreased synovial thickness, and reduced the OARSI OA score without an effect on the meniscus and osteophyte maturity scores at 8 weeks post-injury. In conclusion, the IL-1Ra-M2 macrophage treatment, given before or after OA was developed, delayed OA progression, indicating that the M2 macrophage-based adoptive gene transfer strategy for OA is tenable. Full article

Osteoarthritis (OA) is the most common chronic arthropathy worldwide. OA synovitis is a common feature that predicts the development and progression of symptoms and joint damage. Although the OA synovium is a target for novel therapies, the development of ex vivo models remains an area requiring further research. We aim to develop a 3D tissue explant culture model of human OA synovium that preserves the architecture and cellular heterogeneity of the original tissue in vitro. We derived tissue explant models from seven patients with OA and followed the culture for up to 10 days, assessing their morphology and cellular composition by immunohistochemistry (IHC) and flow cytometry, respectively. IHC analysis of explant cultures showed that tissue integrity and viability were maintained in our in vitro system. Furthermore, cellular heterogeneity was essentially unchanged when considering CD4⁺ T cells, CD8⁺ T cells, and myeloid fractions in our model. No significant variation was observed in the CD90⁺ and CD90^-CD55⁺ fractions, which also maintained an activated state as indicated by high levels of FAP expression. An ex vivo OA synovial tissue explant model can maintain pathological tissue integrity for 10 days in culture. This simple and reliable culture system may be useful for analyzing the pathogenesis of OA disease and for the development and testing of therapeutic drugs. Full article

Background/Objectives: Degenerative joint diseases (DJDs) involve intricate molecular disruptions within bone, cartilage, and synovial tissues, often preceding overt radiographic changes. These tissues exhibit complex biomolecular architectures and their degeneration leads to microstructural disorganization and inflammation that are challenging to detect with conventional imaging techniques. This review aims to synthesize recent advances in imaging, computational modeling, and sequencing technologies that enable high-resolution, non-invasive characterization of joint tissue health. Methods: We examined advanced modalities including high-resolution MRI (e.g., T1ρ, sodium MRI), quantitative and dual-energy CT (qCT, DECT), and ultrasound elastography, integrating them with radiomics, deep learning, and multi-scale modeling approaches. We also evaluated RNA-seq, spatial transcriptomics, and mass spectrometry-based proteomics for omics-guided imaging biomarker discovery. Results: Emerging technologies now permit detailed visualization of proteoglycan content, collagen integrity, mineralization patterns, and inflammatory microenvironments. Computational frameworks ranging from convolutional neural networks to finite element and agent-based models enhance diagnostic granularity. Multi-omics integration links imaging phenotypes to gene and protein expression, enabling predictive modeling of tissue remodeling, risk stratification, and personalized therapy planning. Conclusions: The convergence of imaging, AI, and molecular profiling is transforming musculoskeletal diagnostics. These synergistic platforms enable early detection, multi-parametric tissue assessment, and targeted intervention. Widespread clinical integration requires robust data infrastructure, regulatory compliance, and physician education, but offers a pathway toward precision musculoskeletal care. Full article