Search Results (951)

Osteoarthritis (OA) is a debilitating joint disease characterized by cartilage degradation, leading to pain and functional impairment. A key contributor to OA progression is the decline in cartilage lubrication. In physiological conditions, synovial fluid (SF) macromolecules like hyaluronic acid (HA), phospholipids, and lubricin play a crucial role in the boundary lubrication of articular cartilage. In early OA, cartilage damage triggers inflammation, altering SF composition and compromising the lubrication layer. This increases friction between mating interfaces, worsening cartilage degradation and local inflammation. Therefore, early-stage restoration of lubrication (by injecting in the joint different classes of compounds and formulations) could alleviate, and potentially reverse, OA progression. In the light of this, a broad variety of lubricants have been investigated for their ability to reduce friction in OA joints and promote cartilage repair in clinical and preclinical studies. This review examines recent advancements in lubricant-based therapy for OA, focusing on natural, bioinspired, and alternative products. Starting from the currently applied therapy, mainly based on natural lubricants as HA, we will present their modified versions, either in hydrogel form or with specific biomimetic moieties with the aim of reducing their clearance from the joint and of enhancing their lubricating properties. Finally, the most advanced and recent formulation, represented by alternative strategies, will be proposed. Particular emphasis will be placed on those ones involving new types of hydrogels, microparticles, nanoparticles, and liposomes, which are currently under investigation in preclinical studies. The potential application of particles and liposomes could foster the transition from natural lubricants to Drug Delivery Systems (DDSs) with lubricant features; transition which could provide more complete OA treatments, by simultaneously providing lubrication replacement and sustained release of different payloads and active agents directly at the joint level. Within each category, we will examine relevant preclinical studies, highlighting challenges and future prospects. Full article

Background: Hesperetin, a flavonoid derived from citrus fruits, exhibits potent antioxidant and anti-inflammatory activities and has been implicated in cartilage protection. However, its effectiveness against T-2 toxin-induced knee cartilage damage remains unclear. Methods: In this study, high-throughput sequencing analysis was employed to identify the key signaling pathways involved in T-2 toxin-induced articular cartilage damage in rats. Animal models were divided into the following groups: control, low-dose T-2 toxin, high-dose T-2 toxin, T-2 toxin + hesperetin, hesperetin, and vehicle. Pathological staining and immunohistochemistry were used to assess pathological changes, as well as the expression levels of the cartilage matrix-related proteins MMP13 and collagen II, along with the activation of the p38 MAPK signaling pathway. Additionally, primary rat chondrocytes were cultured to establish an in vitro model for investigating the underlying mechanism. Results: High-throughput sequencing analysis revealed the involvement of the MAPK signaling pathway in T-2 toxin-induced articular cartilage damage in rats. Hesperetin intervention in T-2 toxin-exposed rats attenuated pathological cartilage damage. Immunohistochemistry results demonstrated a significant reduction in collagen II protein expression in the high-dose T-2 toxin group (p < 0.01), accompanied by a significant increase in MMP13 protein expression (p < 0.01). In both the articular cartilage and the epiphyseal plate, the T-2 toxin + hesperetin group exhibited significantly higher collagen II protein expression than the high-dose T-2 toxin group (p < 0.05), along with significantly lower MMP13 protein expression (p < 0.05). Hesperetin inhibited the over-activation of the p38/MEF2C signaling axis induced by T-2 toxin in primary rat chondrocytes. Compared to the T-2 toxin group, the T-2 toxin + hesperetin group showed significantly reduced phosphorylation levels of p38 and protein expression levels of MEF2C (p < 0.001 or p < 0.05). Moreover, the T-2 toxin + hesperetin group exhibited a significant decrease in MMP13 protein expression (p < 0.05) and a significant increase in collagen II protein expression (p < 0.01) compared to the T-2 toxin group. Conclusions: T-2 toxin activates the p38 MAPK signaling pathway, causing knee cartilage damage in rats. Treatment with hesperetin inhibits the p38/MEF2C signaling axis, regulates collagen II and MMP13 protein expression, and reduces cartilage injury significantly. Full article

Hemophilia, which is a rare disease, results from congenital deficiencies of coagulation factors VIII and IX, respectively, leading to spontaneous bleeding into joints, resulting in hemophilic arthropathy (HA). HA involves complex processes, including synovial proliferation, angiogenesis, and tissue remodeling. Despite ongoing research, factors contributing to HA progression, especially in adults with severe HA experiencing joint pain, remain unclear. Blood markers, particularly collagen-related ones, have been explored to assess joint health in hemophilia. For example, markers like CTX-I and CTX-II reflect bone and cartilage turnover, respectively. Studies indicate elevated levels of certain markers post-bleeding episodes, suggesting joint health changes. However, longitudinal studies on collagen turnover and basement membrane or endothelial cell markers in relation to joint outcomes, particularly during painful episodes, are scarce. Given the role of the CX3CL1/CX3XR1 axis in arthritis, other studies investigate its involvement in HA. The importance of different inflammatory and bone damage biomarkers should be assessed, alongside articular cartilage and synovial membrane morphology, aiming to enhance understanding of hemophilic arthropathy progression. Full article

Knee osteoarthritis (KOA) is a musculoskeletal disorder characterized by articular cartilage degeneration and chronic inflammation, affecting one in five people over 40 years old. The purpose of this study was to provide an overview of traditional and novel minimally invasive treatment options and role of artificial intelligence (AI) to streamline the diagnostic process of KOA. This literature review provides insights into the mechanisms of action, efficacy, complications, technical approaches, and recommendations to intra-articular injections (corticosteroids, hyaluronic acid, and plate rich plasma), genicular artery embolization (GAE), and genicular nerve ablation (GNA). Overall, there is mixed evidence to support the efficacy of the intra-articular injections that were covered in this study with varying degrees of supported recommendations through formal medical societies. While GAE and GNA are more novel therapeutic options, preliminary evidence supports their efficacy as a potential minimally invasive therapy for patients with moderate to severe KOA. Furthermore, there is evidentiary support for the use of AI to assist clinicians in the diagnosis and potential selection of treatment options for patients with KOA. In conclusion, there are many exciting advancements within the diagnostic and treatment space of KOA. Full article

Background: Osteoarthritis (OA) is a complex disease marked by the degradation of articular cartilage. Objective: This study aimed to explore the relationship between cartilage volume/thickness and clinical outcomes in knee OA patients treated with intra-articular injections over one year. Methods: Twenty-four patients with mild-to-moderate OA were retrospectively analyzed using knee MRI. OA features were assessed semiquantitatively with the Whole-Organ Magnetic Resonance Imaging Score (WORMS), while cartilage thickness and volume in the medial femoral condyle (MFC) and medial tibial plateau (MTP) were measured. T1ρ and T2 values for MFC cartilage were also recorded. Clinical outcomes were evaluated using the Korean Western Ontario and McMaster Universities (K-WOMAC) and Knee Injury Osteoarthritis Outcomes (KOOS) scores. Spearman’s rank test assessed the associations between imaging changes and clinical outcomes. Results: The baseline MTP and MFC cartilage thickness and MTP cartilage volume showed significant correlations with clinical outcomes. Additionally, less progressive cartilage loss in the medial femorotibial joint (MFTJ) and overall joint was linked to a better clinical response over 12 months. Conclusions: In conclusion, thicker baseline MFTJ cartilage and minimal cartilage loss were associated with favorable clinical outcomes in knee OA patients receiving intra-articular injections. Full article

Treating cartilage damage is challenging as its ability for self-regeneration is limited. Left untreated, it can progress to osteoarthritis (OA), a joint disorder characterized by the deterioration of articular cartilage and other joint tissues. Surgical options, such as microfracture and cell/tissue transplantation, have shown promise as techniques to harness the body’s endogenous regenerative capabilities to promote cartilage repair. Nonetheless, these techniques have been scrutinized due to reported inconsistencies in long-term outcomes and the tendency for the defects to regenerate as fibrocartilage instead of the smooth hyaline cartilage native to joint surfaces. Orthobiologics are medical therapies that utilize biologically derived substances to augment musculoskeletal healing. These treatments are rising in popularity because of their potential to enhance surgical standards of care. More recent developments in orthobiologics have focused on the role of exosomes in articular cartilage repair. Exosomes are nano-sized extracellular vesicles containing cargo such as proteins, lipids, and nucleic acids, and are known to facilitate intercellular communication, though their regenerative potential still needs to be fully understood. This review aims to demonstrate the advancements in cartilage regeneration, highlight surgical and biological treatment options, and discuss the recent strides in understanding the precise mechanisms of action involved. Full article

Thioredoxin-interacting protein (TXNIP) has been involved in oxidative stress and activation of the NOD-like receptor protein-3 (NLRP3) inflammasome, directly linking it to the pyroptosis pathway. Furthermore, pyroptosis may contribute to the inflammatory process in osteoarthritis (OA). The purpose of this study was to investigate the role of TXNIP in activating the NLRP3 inflammasome through the pyroptosis pathway in an OA rat model. Destabilization of the medial meniscus (DMM) was induced in the OA model with intra-articular injections of adeno-associated virus (AAV) overexpressing (OE) or knocking down (KD) TXNIP. A total of 48 healthy rats were randomly divided into six groups (N = 8 each). During the experiment, the rats’ weights, mechanical pain thresholds, and thermal pain thresholds were measured weekly. Morphology staining, micro-CT, 3D imaging, and immunofluorescence (IF) staining were used to measure the expression level of TXNIP, and ELISA techniques were employed. OE-TXNIP-AAV in DMM rats aggravated cartilage destruction and subchondral bone loss, whereas KD-TXNIP slowed the progression of OA. The histological results showed that DMM modeling and OE-TXNIP-AAV intra-articular injection caused joint structure destruction, decreased anabolic protein expression, and increased catabolic protein expression and pyroptosis markers. Conversely, KD-TXNIP-AAV slowed joint degeneration. OE-TXNIP-AVV worsened OA by accelerating joint degeneration and damage, while KD-TXNIP-AAV treatment had a protective effect. Full article

Objectives: The purpose of this study was to prospectively investigate the progression of cartilage thinning in patients with symptomatic rotator cuff tears using MRI. Methods: Two hundred twenty-five consecutive patients with symptomatic rotator cuff tears visited our institute between 2009 and 2019. Of these, 28 shoulders of 27 patients (mean age, 65 years) who underwent at least two magnetic resonance imaging (MRI) examinations were prospectively enrolled. They all received conservative treatment. The mean follow-up was 67 months. Changes in cartilage thickness and the combined cartilage and subchondral bone thickness at the initial and final MRI were measured using a RadiAnt DICOM-viewer (Medixant, Poznan, Poland). The cartilage thickness of the humeral head was measured in the oblique coronal and sagittal images. The glenoid cartilage was measured in the axial and oblique coronal images. Results: At an average period of 5 years, 12 of 28 shoulders (42%) showed more than a 30% decrease in cartilage thickness in the humeral head. The glenoid showed cartilage thinning in only one shoulder (4%). In the humeral head, progressive cartilage thinning was seen mainly in the anterior and posterior parts of the humeral head in the sagittal plane. In the glenoid, progressive cartilage thinning was seen on the entire surface except the posterior area. There was no significant difference in cartilage thickness between the first and final follow-ups for both the humeral head and the glenoid. Conclusions: A total of 12 of 28 shoulders (42%) showed more than a 30% decrease in cartilage thickness in the humeral head, which was mainly observed in the anterior and posterior areas of the humeral head. Full article

Phospholipids (PLs), essential components of cell membranes, play significant roles in maintaining the structural integrity and functionality of joint tissues. One of the main components of synovial joint fluid (SJF) is PLs. Structures such as PLs that are found in low amounts in biological fluids may need to be selectively enriched to be analyzed. Monodisperse-mesoporous SiO₂ microspheres were synthesized by a multi-step hydrolysis condensation method for the selective enrichment and separation of PLs in the SJF. The microspheres were characterized by SEM, XPS, XRD, and BET analyses. SiO₂ microspheres had a 161.5 m²/g surface area, 1.1 cm³/g pore volume, and 6.7 nm pore diameter, which were efficient in the enrichment of PLs in the SJF. The extracted PLs with sorbents were analyzed using Q-TOF LC/MS in a gradient elution mode with a C18 column [2.1 × 100 mm, 2.5 μM, Xbridge Waters (Milford, MA, USA)]. An untargeted lipidomic approach was performed, and the phospholipid enrichment was successfully carried out using the proposed solid-phase extraction (SPE) protocol. Recovery of the SPE extraction of PLs using sorbents was compared to the classical liquid–liquid extraction (LLE) procedure for lipid extraction. The results showed that monodisperse-mesoporous SiO₂ microspheres were eligible for selective enrichment of PLs in SJF samples. These microspheres can be used to identify PLs changes in articular joint cartilage (AJC) in physiological and pathological conditions including osteoarthritis (OA) research. Full article

The extracellular matrix of cartilage primarily constitutes of collagen and aggrecan. Cartilage degradation starts with aggrecan loss in osteoarthritis (OA). Vitamin D (VD) plays an essential role in several inflammation-related diseases and can protect the collagen in cartilage during OA. The present study focused on the role of VD in aggrecan turnover of human articular chondrocytes treated with tumor necrosis factor α (TNF-α) and the possible mechanism. Treatment with different doses of VD and different periods of intervention with TNF-α and TGF-β1 receptor (TGFβR1) inhibitor SB525334 were investigated. The viability of human chondrocytes and extracellular secretion of TGF-β1 were measured. The expression of intracellular TGFβR1 and VD receptor was examined. Transcriptional and translational levels of aggrecan and the related metabolic factors were analyzed. The results showed that TNF-α markedly reduced the viability, TGFβR1 expressions and aggrecan levels of human chondrocytes, and increased disintegrin and metalloproteinase with thrombospondin motifs. The alterations were partially inhibited by VD treatment. Furthermore, the effects of VD were blocked by the TGFβR1 inhibitor SB525334 in TNF-α-treated cells. VD may prevent proteoglycan loss due to TNF-α via TGF-β1 signaling in human chondrocytes. Full article

Osteoarthritis (OA) is an age-related disease characterized by inflammation, pain, articular cartilage damage, synovitis, and irreversible disability. Gynostemma pentaphyllum (Thunb.) Makino (GP), a herbal medicine traditionally used in East Asia for its anti-inflammatory properties, was investigated for its potential to modulate OA pathology and symptoms. This study evaluated GP’s efficacy in inhibiting pain, functional decline, and cartilage destruction in monosodium iodoacetate-induced OA and acetic acid-induced writhing models. Additionally, the effects of GP on OA-related inflammatory targets were assessed via mRNA and protein expression in rat knee cartilage and lipopolysaccharide-induced RAW 264.7 cells. The GP group demonstrated significant pain relief, functional improvement, and cartilage protection. Notably, GP inhibited key inflammatory mediators, including interleukin (IL)-1β, IL-6, matrix metalloproteinases (MMP)-3 and MMP-13, cyclooxygenase-2, and prostaglandin E receptor 2, surpassing the effects of active controls. These findings suggest that GP is a promising candidate for disease-modifying OA drugs and warrants further comprehensive studies. Full article

Background/Objectives: To investigate if intra-articular biomarkers relate to peripheral and central sensitization in patients with late-stage knee osteoarthritis (KOA). Methods: A total of 17 (6M, 11F) patients (aged 69 ± 10 years) were assessed for peripheral (pressure pain thresholds (PPT)) and central (temporal summation (TS) and conditioned pain modulation (CPM)) sensitization the day before total knee arthroplasty. Synovial fluid was collected during surgery and assayed for IL-6, IL-8, IL-10, TNF-α, CXCL-10, BDNF, NGF, CCL2, CCL5, VEGF, IL-1RI, MMP-1, MMP-7, IL-1β, and CXCL-9. Associations of biomarkers and their combinations reflecting chronic (CXCL-9) and acute ((CCL2×CXCL-10)/IL-10)) inflammation, cartilage degeneration (MMP-1×MMP-7), and neurotrophy (NGF×BDNF) with PPT, TS, and CPM were analyzed by bivariate correlations and by multiple linear regression analyses corrected for BMI, sex, and age. Results: The medial joint line and the superior medial joint region showed the lowest PPT. Higher acute inflammation related significantly to worse pressure tenderness at the superior medial joint region (R² = 0.642; p = 0.010). Cartilage degeneration and chronic inflammation were associated with both absolute (R² = 0.827; p = 0.001) and relative CPM (R² = 0.882; p < 0.001). Acute inflammation and neurotrophy were related to relative TS at the m. tibialis anterior (R² = 0.728; p = 0.02). Conclusions: This study demonstrates that increased levels of intra-articular biomarkers of acute inflammation are related to peripheral sensitization and that biomarkers of cartilage degeneration and chronic inflammation are associated with central sensitization. These results may be a stepping-stone toward a better understanding of the working mechanism of peripheral and central sensitization in KOA pain and the development of more targeted therapeutic interventions. Full article

The global cases of knee osteoarthritis (KOA) are projected to increase by 74.9% by 2050. Currently, over half of patients remain dissatisfied with their pain relief. This review addresses unmet needs for moderate-to-severe KOA pain; it offers evidence and insights for improved management. Italian experts from the fields of rheumatology, physical medicine and rehabilitation, orthopedics, primary care, and pain therapy have identified several key issues. They emphasized the need for standardized care protocols to address inconsistencies in patient management across different specialties. Early diagnosis is crucial, as cartilage responds better to early protective and structural therapies. Faster access to physiatrist evaluation and reimbursement for physical, rehabilitative, and pharmacological treatments, including intra-articular (IA) therapy, could reduce access disparities. Concerns surround the adverse effects of oral pharmacological treatments, highlighting the need for safer alternatives. Patient satisfaction with corticosteroids and hyaluronic acid-based IA therapies reduces over time and there is no consensus on the optimal IA therapy protocol. Surgery should be reserved for severe symptoms and radiographic KOA evidence, as chronic pain post-surgery poses significant societal and economic burdens. The experts advocate for a multidisciplinary approach, promoting interaction and collaboration between specialists and general practitioners, to enhance KOA care and treatment consistency in Italy. Full article

Articular cartilage receives nutrients and oxygen from the synovial fluid to maintain homeostasis. However, compared to tissues with abundant blood flow, articular cartilage is exposed to a hypoxic environment (i.e., physioxia) and has an enhanced hypoxic stress response. Hypoxia-inducible factors (HIFs) play a pivotal role in this physioxic environment. In normoxic conditions, HIFs are downregulated, whereas in physioxic conditions, they are upregulated. The HIF-α family comprises three members: HIF-1α, HIF-2α, and HIF-3α. Each member has a distinct function in articular cartilage. In osteoarthritis, which is primarily caused by degeneration of articular cartilage, HIF-1α is upregulated in chondrocytes and is believed to protect articular cartilage by acting anabolically on it. Conversely, in contrast to HIF-1α, HIF-2α exerts a catabolic influence on articular cartilage. It may therefore be possible to develop a new treatment for OA by controlling the expression of HIF-1α and HIF-2α with drugs or by altering the oxygen environment in the joints. Full article

Introduction: Osteoarthritis is a degenerative condition of the cartilage, often common among the population and occurs frequently with aging. Many factors are decisive for the development of its pathogenesis such as age, obesity, trauma, mechanical load, and modification of synovial biology. The main features of osteoarthritis are chondrocytes and cartilage matrix loss, which lead to pain, loss of function of the whole joint, and disability, representing a relevant health problem. Recently, a new therapeutic approach based on cell therapy has been studying the regenerative ability of mesenchymal stem cells for osteoarthritic chondrocytes. Aim: This in vitro study clarifies the regenerative effects of multipotent adipose-derived stem cells and the pluripotent amniotic epithelial stem cells on arthrosis chondrocytes by performing co-culture experiments. Methods: We studied the regenerative potential of secretome (soluble factors and extracellular vesicles), mesenchymal stem cells, and the adipose stromal vascular fraction. The regenerative effects were evaluated by gene and protein expression analysis of articular cartilage-specific genes and proteins like col2a1, acan, and sox9. Results: Mesenchymal stem cells, secretome, and adipose stromal vascular fractions influenced the cartilage genes and protein expression. Conclusions: The results indicate that the treatment with mesenchymal stem cells could be the best biological approach for cartilage regenerative medicine. Full article