Search Results (549)

Background/Objectives: Degenerative processes of the hip joint increasingly affect not only the articular cartilage but also periarticular structures such as the joint capsule and acetabular labrum. This study aimed to investigate the structural and molecular changes occurring in these tissues during advanced hip osteoarthritis. Methods: A combined analysis using immunohistochemistry (IHC), scanning electron microscopy (SEM), and micro-computed tomography (microCT) was conducted on tissue samples from patients undergoing total hip arthroplasty and from controls with morphologically normal joints. Markers associated with proliferation (Ki67), inflammation (CD68), angiogenesis (CD31, ERG), chondrogenesis (SOX9), and lubrication (Lubricin) were evaluated. Results: The pathological group showed increased expression of Ki67, CD68, CD31, ERG, and SOX9, with a notable decrease in Lubricin. SEM analysis revealed ultrastructural disorganization, collagen fragmentation, and neovascular remodeling in degenerative samples. A significant correlation between structural damage and molecular expression was identified. Conclusions: These results suggest that joint capsule and acetabular labrum degeneration are interconnected and reflect a broader pathophysiological continuum, supporting the use of integrated IHC and SEM profiling for early detection and targeted intervention in hip joint disease. 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

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 a leading cause of disability worldwide and is characterized by the gradual degradation of articular cartilage in weight-bearing joints, notably the knees and hips. However, the primary morphological and anatomical determinants of the disease onset and progression remain unclear. This narrative overview examines how variations in cartilage thickness—traditionally viewed as a biomechanical protective feature—can paradoxically compromise metabolic homeostasis during prolonged sedentary behavior. Intriguingly, compelling evidence suggests that despite its superior load-bearing capacity, thicker cartilage faces greater challenges in solute transport, a limitation further exacerbated by the formation of diffusion-resistant boundary layers at the cartilage–fluid interface during immobilization. This phenomenon restricts nutrient influx and impedes waste clearance, leading to the accumulation of catabolic byproducts in deep cartilage zones and accelerated extracellular matrix breakdown, potentially influencing OA pathogenesis. By critically synthesizing current debates on mechanical loading with emerging data on metabolic dysregulation, particularly nutrient diffusion limitations, this analysis underscores the urgent need for targeted investigation of synovial–cartilage interface dynamics and chondrocyte metabolism under low-motion conditions. This study further advocates for strategic research focusing on often-overlooked, silent metabolic imbalances among sedentary populations and recommends early-intervention strategies, such as periodic joint mobilization, ergonomic adaptations, and public-health campaigns, to reduce prolonged sitting, preserve joint function, and guide more effective prevention and management approaches for non-traumatic OA in contemporary contexts. Full article

Osteoarthritis (OA) is the most common degenerative joint disease, characterized by articular cartilage degradation, synovial inflammation, and ligament lesions. Non-coding RNAs (ncRNAs) do not encode any protein products and play a fundamental role in regulating gene expression in several physiological processes, such as in the regulation of cartilage homeostasis. When deregulated, they affect the expression of genes involved in cartilage degradation and synovial inflammation, contributing to the onset and progression of OA. Oxidative stress is also involved in the pathogenesis of OA by contributing to the inflammatory response, degradation of the extracellular matrix, and induction of chondrocyte apoptosis. Studies in the literature show a reciprocal relationship between the altered expression of a number of ncRNAs, including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), and oxidative stress. The aim of this review is to highlight the role of oxidative stress, miRNAs, and lncRNAs and their cross-talk in OA in order to understand the main molecular mechanisms involved and to identify possible targets that may be useful for the identification and development of new diagnostic and therapeutic approaches for this disease. 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/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

Background/Objectives: Recombinant Fc proteins have been produced that have a protective effect in mouse models of arthritis, such as the K/BxN rheumatoid arthritis model. We have previously shown that a recombinant human IgG1 Fc with a point mutation at position 309, replacing a leucine with a cysteine, fused to the human IgM tailpiece to form a human IgG1 Fc hexamer, rFc-µTP-L309C, effectively prevents neutrophil infiltration into the joints and ameliorates arthritis in the K/BxN serum transfer model and in the endogenous chronic arthritis K/BxN model. We have now investigated the effect of rFc-µTP-L309C on T-cells in the K/BxN chronic arthritis mouse model. Methods: PBMCs were isolated from the spleen, lymph nodes and joint synovial fluid from K/BxN mice having severe chronic arthritis that had been treated with 200 mg/kg rFc-µTP-L309C or human serum albumin (HSA). Flow cytometry was used to isolate the activated CD4⁺CD44⁺ T-cells and T-regulatory cells (Tregs). Intracellular staining was used to identify Th1 and Th17 T-cell subsets, and CD4⁺CD25⁺FoxP3⁺ Tregs. ELISA was used to measure levels of IL-10 and TGF-β in synovial fluid. Results: We find that amelioration of the arthritis occurs after treatment with rFc-µTP-L309C and results in a decrease in Th1 cells’ production of IFNγ and Th17 cells’ production of IL-17. Amelioration also results in decreased production of GM-CSF. Moreover, amelioration results in increased Tregs and IL-10 production in the synovial fluid. Conclusions: rFc-µTP-L309C reduces the inflammatory T-cells and increases the regulatory anti-inflammatory T-cells in the chronic arthritis K/BxN mouse model. This effect explains, in part, the ability of rFc-µTP-L309C to ameliorate the arthritis and reduce damage on the articular cartilage of K/BxN mice. Full article

Collagen II is a vital structural component in developing bones and mature cartilage. Mutations in this protein cause spondyloepiphyseal dysplasia, a disease characterized primarily by altered skeletal growth and manifesting with a range of phenotypes, from lethal to mild. This study examined transgenic mice harboring the R992C (p.R1124C) substitution in collagen II. Previous research demonstrated significant growth abnormalities and disorganized growth plate structure in these mice, and histological signs of osteoarthritic changes in the knee joints of 9-month-old mice with the R992C mutation. Our study focuses on detecting early structural changes in the articular cartilage that occur before histological signs become apparent. Through microscopic and spectroscopic analyses, we observed significant alterations in the distribution gradients of collagenous proteins and proteoglycans in the cartilage of R992C mutant mice. We propose that these early changes, eventually leading to articular cartilage degeneration in older mice, underscore the progressive nature of osteoarthritic changes linked to collagen II mutations. By identifying these early structural aberrations, our findings emphasize the importance of early detection of osteoarthritic changes, potentially facilitating timely, non-surgical interventions. Full article

Articular cartilage (AC) plays an important role in the biomechanics of synovial joints. Its task is to enable smooth movement and transfer of mechanical loads with minimised friction. AC is characterised by unique mechanical properties resulting from its complex structure, in which the dominant components are type II collagen, proteoglycans and water. Healthy articular cartilage shows elasticity in compression, viscoelastic properties, and the ability to relax stresses under the influence of cyclic loads. In response to different loading modes, it shows anisotropic and non-uniform behaviour, which translates into its cushioning and protective function for the subchondral bone. Significant changes occur in the structure and mechanical properties of cartilage with age as a result of mechanical overload or degenerative diseases, such as osteoarthritis. This results in a deterioration of the cushioning and mechanical function, which leads to progressive degradation of joint tissues. Understanding the mechanical properties of AC is crucial for developing effective diagnostic methods. Analysis of changes in mechanical properties contributes to the early detection of pathological changes. The aim of this paper is to review the current state of knowledge regarding the structure and biomechanical properties of articular cartilage, and to analyse conventional and alternative diagnostic methods in the context of their suitability for assessing the state of AC, particularly in the early stages of degenerative processes. Full article

Osteoarthritis (OA) is now widely recognized not merely as a cartilage-centric disease but as a multifactorial disorder affecting the entire joint as an organ, including the articular cartilage, subchondral bone, synovium, ligaments, menisci, and the innervating neural elements. This review explores the complex pathophysiology of OA with a focus on the emerging mechanisms of pain and inflammation that extend beyond articular cartilage degradation. Joint inflammation driven by immune activation in response to cellular stress signals promotes the release of pro-inflammatory mediators and catabolic enzymes. Key signaling pathways such as NF-κB, MAPKs, and JAK/STAT amplify these responses, and pain is sustained through peripheral and central sensitization, contributing to exacerbating symptoms even in the absence of visible joint damage. This review also integrates molecular and cellular mechanisms to highlight innovative therapies aimed at modifying both the structural damage and neurosensory drivers of pain. These approaches offer the potential to not only alleviate symptoms but also alter disease progression, signaling a move toward personalized, mechanism-based treatments. Given the intricate interactions among joint tissues, immune activation, and sensory processing, a comprehensive strategy that targets both structural degeneration and neuroinflammation is essential for the future of OA management. Emphasizing the joint as an integrated organ, we advocate for translational research linking molecular pathology with clinically meaningful outcomes. Full article

Understanding the complex mechanical behavior of osteochondral tissues in silico is essential for improving experimental models and advancing research in joint health and degeneration. This review provides a comprehensive analysis of the constitutive models currently used to represent the different layers of the osteochondral region, from articular cartilage to subchondral bone, including intermediate regions such as the tidemark and the calcified cartilage layer. Each layer exhibits unique structural and mechanical properties, necessitating a layer-specific modeling approach. Through critical comparison of existing mathematical models, the viscoelastic model is suggested as a pragmatic starting point for modeling articular cartilage zones, the tidemark, and the calcified cartilage layer, as it captures essential time-dependent behaviors such as creep and stress relaxation while ensuring computational efficiency for initial coupling studies. On the other hand, a linear elastic model was identified as an optimal starting point for both the subchondral bone plate and the subchondral trabecular bone, reflecting their dense and stiff nature, and providing a coherent framework for early-stage multilayer integration. This layered modeling approach enables the development of physiologically coherent and computationally efficient representations of osteochondral region modeling. Furthermore, by establishing a layer-specific modeling approach, this review paves the way for modular in silico simulations through the coupling of computational models. Such an integrative framework supports scaffold design, in vitro experimentation, preclinical validation, and the mechanobiological exploration of osteochondral degeneration and repair. These efforts are essential for deepening our understanding of tissue responses under both physiological and pathological conditions. Ultimately, this work provides a robust theoretical foundation for future in silico and in vitro studies aimed at advancing osteochondral tissue regeneration strategies. Full article

Current intra-articular therapies with hyaluronic acid (HA) provide symptomatic relief in joint diseases, but have limited efficacy in counteracting oxidative stress and inflammation, key drivers of cartilage degradation in rheumatoid arthritis (RA). To address this limitation, the potential of combining HA with the phytochemicals xanthohumol (XAN) and epigallocatechin-3-O-gallate (EGCG), known for their antioxidant and anti-inflammatory properties, was evaluated in a cellular model of RA (SW982 synoviocytes stimulated with interleukin-1β, IL-1β). The Chou–Talalay method demonstrated that their combination synergistically reduced reactive oxygen species (ROS) and nitric oxide (NO) levels. The “TRIPLE” combination (HA + XAN + EGCG) showed the lowest combination index and the highest dose reduction index. Compared to individual treatments, TRIPLE significantly decreased IL-1β-induced IL-6, IL-8, TNF-α, and MMP-3 levels, while increasing the levels of the anti-inflammatory cytokine IL-10. Western blot analysis revealed a marked reduction in iNOS, COX-2, and MMP-3 protein expression following TRIPLE treatment. Moreover, the combination inhibited IL-1β-induced phosphorylation of IκB and p65, thereby preventing NF-κB activation. These findings suggest that integrating XAN and EGCG into injectable HA formulations may represent a promising strategy to improve the management of joint inflammation in RA. Full article

Articular cartilage is an avascular and aneural connective tissue that is frequently damaged due to trauma or degenerative joint diseases, often resulting in arthritis. Its limited intrinsic capacity for self-renewal poses a significant challenge to effective repair. Hence, the development of regenerative strategies is essential to enhance the poor intrinsic healing of cartilage tissue. Photobiomodulation (PBM) has gained increasing attention as a noninvasive, drug-free, and safe approach. PBM exerts photobiological effects that promote cellular responses and reduce inflammatory conditions, all of which are beneficial for cartilage repair. Nonetheless, the efficacy of PBM varies depending on treatment parameters and treated targets. This review first summarizes PBM parameter-dependent outcomes in cartilage regeneration studies. Reported data indicate frequent use of red lasers (600–660 nm, 0–10 J/cm²), GaAIAs lasers (800–880 nm, 10–50 J/cm²), and Nd:YAG lasers (1064 nm, up to 200 J/cm²) in in vitro, in vivo, and clinical studies. Moreover, PBM in conjunction with cartilage tissue engineering (CTE) has shown synergistic effects, enhancing scaffold-based repair outcomes. This review additionally explores PBM applications within CTE frameworks. The summarized findings aim to inform researchers and physicians by outlining optimized PBM strategies and highlighting PBM’s strong potential in promoting cartilage regeneration, both independently and in combination with CTE. Full article

Synovial inflammation is recognised as a pathological driver of osteoarthritis (OA), a degenerative joint disease involving cartilage degradation and joint pain. Since extracellular vesicles (EVs) have emerged as key mediators of cellular cross-talk, this study characterised synovial fluid EVs (SFEVs) in OA patients with varying disease severity and determined their functional effects on OA articular chondrocytes. Synovial fluid and articular cartilage were collected from patients undergoing knee surgery. SFEVs were isolated via ultracentrifugation and characterised by nanoparticle tracking analysis, ExoView, and Luminex analysis of protein cargo. Patients were stratified into mild/moderate- and severe-OA groups based on Oxford Knee Score and EQ5D. Chondrocytes were treated with SFEVs, and transcriptomic and secretome responses were analysed using RNA sequencing, Luminex, and ELISA. SFEVs from patients with severe OA were more abundant, smaller and exhibited increased tetraspanin expression. Synovial fluid and SFEVs induced distinct transcriptomic changes in chondrocytes. SFEVs from patients with severe OA promoted a pro-inflammatory and catabolic chondrocyte phenotype, with upregulation of CRTAC1, COL6A3, TNC, and CXCL5, greater secretion of IL-6, MMP1, MMP3 and MMP13, and pro-nociceptive mediators (NGF and Substance P). These findings suggest that SFEVs may contribute to OA progression by exacerbating cartilage damage and promoting pain sensitisation. Full article