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Magma (New York, N.Y.) Jun 2024Osteoarthritis (OA) is a disabling chronic disease involving the gradual degradation of joint structures causing pain and dysfunction. Magnetic resonance imaging (MRI)... (Review)
Review
Osteoarthritis (OA) is a disabling chronic disease involving the gradual degradation of joint structures causing pain and dysfunction. Magnetic resonance imaging (MRI) has been widely used as a non-invasive tool for assessing OA-related changes. While anatomical MRI is limited to the morphological assessment of the joint structures, quantitative MRI (qMRI) allows for the measurement of biophysical properties of the tissues at the molecular level. Quantitative MRI techniques have been employed to characterize tissues' structural integrity, biochemical content, and mechanical properties. Their applications extend to studying degenerative alterations, early OA detection, and evaluating therapeutic intervention. This article is a review of qMRI techniques for musculoskeletal tissue evaluation, with a particular emphasis on articular cartilage. The goal is to describe the underlying mechanism and primary limitations of the qMRI parameters, their association with the tissue physiological properties and their potential in detecting tissue degeneration leading to the development of OA with a primary focus on basic and preclinical research studies. Additionally, the review highlights some clinical applications of qMRI, discussing the role of texture-based radiomics and machine learning in advancing OA research.
PubMed: 38904746
DOI: 10.1007/s10334-024-01174-7 -
International Journal of Biological... 2024Osteoarthritis (OA) is a challenging degenerative joint disease to manage. Previous research has indicated that cell-free fat extract (CEFFE) may hold potential for OA...
Osteoarthritis (OA) is a challenging degenerative joint disease to manage. Previous research has indicated that cell-free fat extract (CEFFE) may hold potential for OA treatment. This study investigated the role of Annexin A5 (AnxA5) within CEFFE in regulating macrophage polarization and protecting chondrocytes. experiments demonstrated that AnxA5 effectively inhibited M1 macrophage polarization by facilitating toll-like receptor (TLR) 4 internalization and lysosomal degradation through calcium-dependent endocytosis. This process decreased TLR4 expression, suppressed pro-inflammatory mediator release, and reduced the production of reactive oxygen species. Furthermore, AnxA5 displayed protective effects against chondrocyte necrosis and apoptosis. studies revealed that intra-articular administration of AnxA5 ameliorated pain symptoms in a monosodium iodoacetate-induced osteoarthritis rat model. Histological analyses indicated a decrease in synovial inflammation and mitigation of cartilage damage following AnxA5 treatment. These results underscored the potential of AnxA5 as a therapeutic option for OA due to its capacity to regulate macrophage polarization and maintain chondrocyte viability. Further investigation into the specific mechanisms and clinical applications of AnxA5 may help improve the management of OA.
Topics: Animals; Osteoarthritis; Rats; Macrophages; Annexin A5; Chondrocytes; Rats, Sprague-Dawley; Male; Toll-Like Receptor 4; Mice; RAW 264.7 Cells; Reactive Oxygen Species; Apoptosis
PubMed: 38904008
DOI: 10.7150/ijbs.92802 -
Regenerative Biomaterials 2024Cartilage tissues possess an extremely limited capacity for self-repair, and current clinical surgical approaches for treating articular cartilage defects can only...
Cartilage tissues possess an extremely limited capacity for self-repair, and current clinical surgical approaches for treating articular cartilage defects can only provide short-term relief. Despite significant advances in the field of cartilage tissue engineering, avoiding secondary damage caused by invasive surgical procedures remains a challenge. In this study, injectable cartilage microtissues were developed through 3D culture of rat bone marrow mesenchymal stem cells (BMSCs) within porous gelatin microcarriers (GMs) and induced differentiation. These microtissues were then injected for the purpose of treating cartilage defects , via a minimally invasive approach. GMs were found to be noncytotoxic and favorable for cell attachment, proliferation and migration evaluated with BMSCs. Moreover, cartilage microtissues with a considerable number of cells and abundant extracellular matrix components were obtained from BMSC-laden GMs after induction differentiation culture for 28 days. Notably, ATDC5 cells were complementally tested to verify that the GMs were conducive to cell attachment, proliferation, migration and chondrogenic differentiation. The microtissues obtained from BMSC-laden GMs were then injected into articular cartilage defect areas in rats and achieved superior performance in alleviating inflammation and repairing cartilage. These findings suggest that the use of injectable cartilage microtissues in this study may hold promise for enhancing the long-term outcomes of cartilage defect treatments while minimizing the risk of secondary damage associated with traditional surgical techniques.
PubMed: 38903559
DOI: 10.1093/rb/rbae064 -
Annals of Biomedical Engineering Jun 2024In order to improve the ability of clinical diagnosis to differentiate articular cartilage (AC) injury of different origins, this study explores the sensitivity of...
In order to improve the ability of clinical diagnosis to differentiate articular cartilage (AC) injury of different origins, this study explores the sensitivity of mid-infrared (MIR) spectroscopy for detecting structural, compositional, and functional changes in AC resulting from two injury types. Three grooves (two in parallel in the palmar-dorsal direction and one in the mediolateral direction) were made via arthrotomy in the AC of the radial facet of the third carpal bone (middle carpal joint) and of the intermediate carpal bone (the radiocarpal joint) of nine healthy adult female Shetland ponies (age = 6.8 ± 2.6 years; range 4-13 years) using blunt and sharp tools. The defects were randomly assigned to each of the two joints. Ponies underwent a 3-week box rest followed by 8 weeks of treadmill training and 26 weeks of free pasture exercise before being euthanized for osteochondral sample collection. The osteochondral samples underwent biomechanical indentation testing, followed by MIR spectroscopic assessment. Digital densitometry was conducted afterward to estimate the tissue's proteoglycan (PG) content. Subsequently, machine learning models were developed to classify the samples to estimate their biomechanical properties and PG content based on the MIR spectra according to injury type. Results show that MIR is able to discriminate healthy from injured AC (91%) and between injury types (88%). The method can also estimate AC properties with relatively low error (thickness = 12.7% mm, equilibrium modulus = 10.7% MPa, instantaneous modulus = 11.8% MPa). These findings demonstrate the potential of MIR spectroscopy as a tool for assessment of AC integrity changes that result from injury.
PubMed: 38902468
DOI: 10.1007/s10439-024-03540-x -
Biomacromolecules Jun 2024Rheumatoid arthritis (RA) is a complicated chronic disorder of the immune system, featured with severe inflammatory joints, synovium hyperplasia, articular cartilage,...
Rheumatoid arthritis (RA) is a complicated chronic disorder of the immune system, featured with severe inflammatory joints, synovium hyperplasia, articular cartilage, and bone damage. In the RA microenvironment, RA-involved cells, overproduced nitric oxide (NO), and pro-inflammatory cytokines are highly interplayed and mutually reinforced, which form a vicious circle and play crucial roles in the formation and progression of RA. To comprehensively break the vicious circle and obtain the maximum benefits, we have developed neutrophil membrane-camouflaged NO scavenging nanoparticles based on an NO-responsive hyaluronic acid derivative for delivery of MTX. These multifunctional nanoparticles (NNO-NPs/MTX), by inheriting the membrane functions of the source cells, possess prolonged circulation and specific localization at the inflamed sites when administrated in the body. Remarkably, NNO-NPs/MTX can neutralize the pro-inflammatory cytokines via the outer membrane receptors, scavenge NO, and be responsively disassociated to release MTX for RA-involved cell regulation and HA for lubrication in the RA sites. In a collagen-induced arthritis mouse model, NNO-NPs/MTX exhibits a significant anti-inflammation effect and effectively alleviates the characteristic RA symptoms such as synovial hyperplasia and cartilage destruction, realizing the synergistic and boosted therapeutic outcome against intractable RA. Thus, NNO-NPs/MTX provides a promising and potent platform to integrately treat RA.
PubMed: 38899740
DOI: 10.1021/acs.biomac.4c00556 -
Journal of ISAKOS : Joint Disorders &... Jun 2024Patellofemoral osteoarthritis (PFOA) is the result of degeneration and loss of articular cartilage of the patella and trochlea, and is a common cause of anterior knee...
Patellofemoral osteoarthritis (PFOA) is the result of degeneration and loss of articular cartilage of the patella and trochlea, and is a common cause of anterior knee pain. PFOA is triggered by insufficient adaptation to overload of the articular cartilage of the PF joint created by abnormal biomechanics. It is important to understand the pathophysiology and natural history to make the diagnosis and to plan treatment. Innate factors including malalignment, patellar instability, kinematic disorders, and acquired factors like trauma, obesity, and endocrine diseases have been found to be causes of PFOA. Genetic predisposition is also described as a contributing cause but without much scientific evidence. The diagnosis will be based on clinical manifestations, such as anterior knee pain aggravated by overloading activities, identification of risk factors, exclusion of referred pain from other pathologies, followed by a systematic and structured physical examination. Imaging will be useful for assessing the presence of early osteoarthritis in the other compartments, for classification of the PFOA, and to identify features to establish an adequate treatment. This paper discusses varying management options for different causes of patellofemoral disease and explains the complexity of the PF joint and its often poorly understood biomechanics.
PubMed: 38897413
DOI: 10.1016/j.jisako.2024.06.004 -
Biomaterials Research 2024The occurrence of rheumatoid arthritis (RA) is highly correlated with progressive and irreversible damage of articular cartilage and continuous inflammatory response....
The occurrence of rheumatoid arthritis (RA) is highly correlated with progressive and irreversible damage of articular cartilage and continuous inflammatory response. Here, inspired by the unique structure of synovial lipid-hyaluronic acid (HA) complex, we developed supramolecular HA-nanomedicine hydrogels for RA treatment by mediating macrophage-synovial fibroblast cross-talk through locally sustained release of celastrol (CEL). Molecular dynamics simulation confirmed that HA conjugated with hydrophobic segments could interspersed into the CEL-loaded [poly(ε-caprolactone--1,4,8-trioxa[4.6]spiro-9-undecanone)-poly(ethylene glycol)-poly(ε-caprolaone--1,4,8-trioxa[4.6]spiro-9-undecanone] (PECT) nanoparticles to form the supramolecular nanomedicine hydrogel HA-poly(ε-caprolactone--1,4,8-trioxa[4.6]spiro-9-un-decanone)/PECT@CEL (HP@CEL), enabling fast hydrogel formation after injection and providing a 3-dimensional environment similar with synovial region. More importantly, the controlled release of CEL from HP@CEL inhibited the macrophage polarization toward the proinflammatory M1 phenotype and further suppressed the proliferation of synovial fibroblasts by regulating the Toll-like receptor pathway. In collagen-induced arthritis model in mice, HP@CEL hydrogel treatment substantial attenuated clinical symptoms and bone erosion and improved the extracellular matrix deposition and bone regeneration in ankle joint. Altogether, such a bioinspired injectable polymer-nanomedicine hydrogel represents an effective and promising strategy for suppressing RA progression through augmenting the cross-talk of macrophages and synovial fibroblast for regulation of chronic inflammation.
PubMed: 38894889
DOI: 10.34133/bmr.0046 -
Journal of Clinical Medicine Jun 2024Degenerative joint disease is a dynamic pathological process characterised by a destabilisation of the degradation and synthesis processes of articular cartilage and...
Degenerative joint disease is a dynamic pathological process characterised by a destabilisation of the degradation and synthesis processes of articular cartilage and subchondral bone layer. Studies suggest that individuals with gonarthrosis experience deficits in proprioception, in addition to changes within their joints, which directly affects their ability to maintain posture and increases their risk of falling. The aim of this study was to assess the functional status of patients with gonarthrosis through a posturographic examination conducted on a stabilometric platform (force plate) and a functional clinical examination. Participants were divided into two groups-a control group ( = 125) and a study group ( = 125). During the qualification process, subjective and objective examinations were conducted, including a functional assessment by means of such tests as the "Up and Go" Test, Functional Reach Test, Five Time Sit to Stand Test, and the Step Test. Subsequently, an assessment was conducted on the force plate by means of a posturographic test-the Romberg test performed with open and closed eyes in a standing position-and balance was evaluated using the Berg Balance Scale. The obtained data were analysed with the use of the IBM SPSS Statistics software version 27.0, by means of the Mann-Whitney test, and correlations were determined by means of Spearman's test. A significance level of = 0.05 was adopted. Statistically significant differences were observed among the assessed groups as a result of both functional and posturographic examinations, along with positive correlations for disease duration, age, and BMI index. Patients with gonarthrosis exhibited disturbances in balance, functionality, and posture compared to healthy individuals in the control group.
PubMed: 38893009
DOI: 10.3390/jcm13113298 -
Nutrients May 2024Osteoarthritis (OA) is a degenerative joint disease characterized by the destruction of the articular cartilage, resulting in a pro-inflammatory response. The... (Review)
Review
Osteoarthritis (OA) is a degenerative joint disease characterized by the destruction of the articular cartilage, resulting in a pro-inflammatory response. The progression of OA is multifactorial and is influenced by the underlying cause of inflammation, which includes but is not limited to trauma, metabolism, biology, comorbidities, and biomechanics. Although articular cartilage is the main tissue affected in osteoarthritis, the chronic inflammatory environment negatively influences the surrounding synovium, ligaments, and subchondral bone, further limiting their functional abilities and enhancing symptoms of OA. Treatment for osteoarthritis remains inconsistent due to the inability to determine the underlying mechanism of disease onset, severity of symptoms, and complicating comorbidities. In recent years, diet and nutritional supplements have gained interest regarding slowing the disease process, prevention, and treatment of OA. This is due to their anti-inflammatory properties, which result in a positive influence on pain, joint mobility, and cartilage formation. More specifically, omega-3 polyunsaturated fatty acids (PUFA) have demonstrated an influential role in the progression of OA, resulting in the reduction of cartilage destruction, inhibition of pro-inflammatory cytokine cascades, and production of oxylipins that promote anti-inflammatory pathways. The present review is focused on the assessment of evidence explaining the inflammatory processes of osteoarthritis and the influence of omega-3 supplementation to modulate the progression of osteoarthritis.
Topics: Humans; Osteoarthritis; Fatty Acids, Omega-3; Dietary Supplements; Cartilage, Articular; Disease Progression; Inflammation; Anti-Inflammatory Agents; Animals
PubMed: 38892583
DOI: 10.3390/nu16111650 -
International Journal of Molecular... Jun 2024Cartilage, a flexible and smooth connective tissue that envelops the surfaces of synovial joints, relies on chondrocytes for extracellular matrix (ECM) production and...
Cartilage, a flexible and smooth connective tissue that envelops the surfaces of synovial joints, relies on chondrocytes for extracellular matrix (ECM) production and the maintenance of its structural and functional integrity. Melatonin (MT), renowned for its anti-inflammatory and antioxidant properties, holds the potential to modulate cartilage regeneration and degradation. Therefore, the present study was devoted to elucidating the mechanism of MT on chondrocytes. The in vivo experiment consisted of three groups: Sham (only the skin tissue was incised), Model (using the anterior cruciate ligament transection (ACLT) method), and MT (30 mg/kg), with sample extraction following 12 weeks of administration. Pathological alterations in articular cartilage, synovium, and subchondral bone were evaluated using Safranin O-fast green staining. Immunohistochemistry (ICH) analysis was employed to assess the expression of matrix degradation-related markers. The levels of serum cytokines were quantified via Enzyme-linked immunosorbent assay (ELISA) assays. In in vitro experiments, primary chondrocytes were divided into Control, Model, MT, negative control, and inhibitor groups. Western blotting (WB) and Quantitative RT-PCR (q-PCR) were used to detect Silent information regulator transcript-1 (SIRT1)/Nuclear factor kappa-B (NF-κB)/Nuclear factor erythroid-2-related factor 2 (Nrf2)/Transforming growth factor-beta (TGF-β)/Bone morphogenetic proteins (BMPs)-related indicators. Immunofluorescence (IF) analysis was employed to examine the status of type II collagen (COL2A1), SIRT1, phosphorylated NF-κB p65 (p-p65), and phosphorylated mothers against decapentaplegic homolog 2 (p-Smad2). In vivo results revealed that the MT group exhibited a relatively smooth cartilage surface, modest chondrocyte loss, mild synovial hyperplasia, and increased subchondral bone thickness. ICH results showed that MT downregulated the expression of components related to matrix degradation. ELISA results showed that MT reduced serum inflammatory cytokine levels. In vitro experiments confirmed that MT upregulated the expression of SIRT1/Nrf2/TGF-β/BMPs while inhibiting the NF-κB pathway and matrix degradation-related components. The introduction of the SIRT1 inhibitor Selisistat (EX527) reversed the effects of MT. Together, these findings suggest that MT has the potential to ameliorate inflammation, inhibit the release of matrix-degrading enzymes, and improve the cartilage condition. This study provides a new theoretical basis for understanding the role of MT in decelerating cartilage degradation and promoting chondrocyte repair in in vivo and in vitro cultured chondrocytes.
Topics: Animals; Sirtuin 1; NF-E2-Related Factor 2; Melatonin; NF-kappa B; Chondrocytes; Signal Transduction; Cartilage, Articular; Transforming Growth Factor beta; Male; Extracellular Matrix; Inflammation
PubMed: 38892389
DOI: 10.3390/ijms25116202