Articular surface integrity assessed by ultrasound is associated with biological characteristics of articular cartilage in early-stage degeneration.
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ABSTRACT:
SUBMITTER: Shi W
PROVIDER: S-EPMC9279397 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:PurposeTo determine the importance of synovial fluid (SF) or subchondral bone marrow (BM) as nutrition sources in cartilage degeneration.MethodsNinety-five-month-old male rabbits were randomly divided into 5 groups according to sources of nutrition: SFBM-both; BM-only; SF-only; None-SFBM; and Free plug (unrestricted). Nutrition to 4-mm-diameter cylindrical osteochondral plugs created on the trochlea of the distal femurs was obstructed by Polyvinyl Chloride (PVC) cap. Cartilage changes were assessed after 4, 8, and 12 weeks by histology, immunohistochemistry, and real-time PCR.ResultsCartilage in the BM-only group suffered the greatest damage, followed by the None-SFBM and SF-only groups. Apoptosis was increased in the BM-only and None-SFBM groups compared with others. Cartilage was significantly thinner at all time points in the BM-only and None-SFBM groups when compared with SFBM-both and Free plug, whereas in the SF-only group, this difference occurred after 8 weeks. Compared with SFBM-both and Free plug, expression of collagen II and aggrecan mRNAs in all groups was decreased but MMP-3 increased, respectively.ConclusionOur data indicate that SF-derived nutrition is the dominant source of sustenance for adult cartilage structure and function. Cartilage damage is observed when the only nutrition source is the BM.
| S-EPMC3717153 | biostudies-literature
Project description:To assess human articular cartilage tissue functionality by serial multiparametric quantitative MRI (qMRI) mapping as a function of histological degeneration. Forty-nine cartilage samples obtained during total knee replacement surgeries were placed in a standardized artificial knee joint within an MRI-compatible compressive loading device and imaged in situ and at three loading positions, i.e. unloaded, at 2.5 mm displacement (20% body weight [BW]) and at 5 mm displacement (110% BW). Using a clinical 3.0 T MRI system (Achieva, Philips), serial T1, T1ρ, T2 and T2* maps were generated for each sample and loading position. Histology (Mankin scoring) and biomechanics (Young's modulus) served as references. Samples were dichotomized as intact (int, n = 27) or early degenerative (deg, n = 22) based on histology and analyzed using repeated-measures ANOVA and unpaired Student's t-tests after log-transformation. For T1ρ, T2 and T2*, significant loading-induced differences were found in deg (in contrast to int) samples, while for T1 significant decreases in all zones were observed, irrespective of degeneration. In conclusion, cartilage functionality may be visualized using serial qMRI parameter mapping and the response-to-loading patterns are associated with histological degeneration. Hence, loading-induced changes in qMRI parameter maps provide promising surrogate parameters of tissue functionality and status in health and disease.
| S-EPMC6459828 | biostudies-literature
Project description:Introduction:Assessment of cartilage integrity during arthroscopy is limited by the subjective visual nature of the technique. To address this shortcoming in diagnostic evaluation of articular cartilage, near infrared spectroscopy (NIRS) has been proposed. In this study, we evaluated the capacity of NIRS, combined with machine learning techniques, to classify cartilage integrity. Methods:Rabbit (n = 14) knee joints with artificial injury, induced via unilateral anterior cruciate ligament transection (ACLT), and the corresponding contra-lateral (CL) joints, including joints from separate non-operated control (CNTRL) animals (n = 8), were used. After sacrifice, NIR spectra (1000-2500 nm) were acquired from different anatomical locations of the joints (n TOTAL = 313: n CNTRL = 111, n CL = 97, n ACLT = 105). Machine and deep learning methods (support vector machines-SVM, logistic regression-LR, and deep neural networks-DNN) were then used to develop models for classifying the samples based solely on their NIR spectra. Results:The results show that the model based on SVM is optimal of distinguishing between ACLT and CNTRL samples (ROC_AUC = 0.93, kappa = 0.86), LR is capable of distinguishing between CL and CNTRL samples (ROC_AUC = 0.91, kappa = 0.81), while DNN is optimal for discriminating between the different classes (multi-class classification, kappa = 0.48). Conclusion:We show that NIR spectroscopy, when combined with machine learning techniques, is capable of holistic assessment of cartilage integrity, with potential for accurately distinguishing between healthy and diseased cartilage.
| S-EPMC7225230 | biostudies-literature
Project description:Osteoarthritis (OA), the most common form of arthritis, is characterized by inflammation of joints and cartilage degradation leading to disability, discomfort, severe pain, inflammation, and stiffness of the joint. It has been shown that adenosine, a purine nucleoside composed of adenine attached to ribofuranose, is enzymatically produced by the human synovium. However, the functional significance of adenosine signaling in homeostasis and pathology of synovial joints remains unclear. Adenosine acts through four cell surface receptors, i.e., A1, A2A, A2B, and A3, and here, we have systematically analyzed mice with a deficiency for A3 receptor as well as pharmacological modulations of this receptor with specific analogs. The data show that adenosine receptor signaling plays an essential role in downregulating catabolic mechanisms resulting in prevention of cartilage degeneration. Ablation of A3 resulted in development of OA in aged mice. Mechanistically, A3 signaling inhibited cellular catabolic processes in chondrocytes including downregulation of Ca2+/calmodulin-dependent protein kinase (CaMKII), an enzyme that promotes matrix degradation and inflammation, as well as Runt-related transcription factor 2 (RUNX2). Additionally, selective A3 agonists protected chondrocytes from cell apoptosis caused by pro-inflammatory cytokines or hypo-osmotic stress. These novel data illuminate the protective role of A3, which is mediated via inhibition of intracellular CaMKII kinase and RUNX2 transcription factor, the two major pro-catabolic regulators in articular cartilage.Key messagesAdenosine receptor A3 (A3) knockout results in progressive loss of articular cartilage in vivo. Ablation of A3 results in activation of matrix degradation and cartilage hypertrophy. A3 agonists downregulate RUNX2 and CaMKII expression in osteoarthritic human articular chondrocytes. A3 prevents articular cartilage matrix degradation induced by inflammation and osmotic fluctuations. A3 agonist inhibits proteolytic activity of cartilage-degrading enzymes.
| S-EPMC8493638 | biostudies-literature
Project description:ObjectiveHuman adult articular cartilage (AC) has little capacity for repair, and joint surface injuries often result in osteoarthritis (OA), characterised by loss of matrix, hypertrophy and chondrocyte apoptosis. Inflammation mediated by interleukin (IL)-6 family cytokines has been identified as a critical driver of proarthritic changes in mouse and human joints, resulting in a feed-forward process driving expression of matrix degrading enzymes and IL-6 itself. Here we show that signalling through glycoprotein 130 (gp130), the common receptor for IL-6 family cytokines, can have both context-specific and cytokine-specific effects on articular chondrocytes and that a small molecule gp130 modulator can bias signalling towards anti-inflammatory and antidegenerative outputs.MethodsHigh throughput screening of 170 000 compounds identified a small molecule gp130 modulator termed regulator of cartilage growth and differentiation (RCGD 423) that promotes atypical homodimeric signalling in the absence of cytokine ligands, driving transient increases in MYC and pSTAT3 while suppressing oncostatin M- and IL-6-mediated activation of ERK and NF-κB via direct competition for gp130 occupancy.ResultsThis small molecule increased proliferation while reducing apoptosis and hypertrophic responses in adult chondrocytes in vitro. In a rat partial meniscectomy model, RCGD 423 greatly reduced chondrocyte hypertrophy, loss and degeneration while increasing chondrocyte proliferation beyond that observed in response to injury. Moreover, RCGD 423 improved cartilage healing in a rat full-thickness osteochondral defect model, increasing proliferation of mesenchymal cells in the defect and also inhibiting breakdown of cartilage matrix in de novo generated cartilage.ConclusionThese results identify a novel strategy for AC remediation via small molecule-mediated modulation of gp130 signalling.
| S-EPMC8444286 | biostudies-literature
Project description:Developmental dysplasia of the hip (DDH) is one of the significant risk factors for hip osteoarthritis. In order to investigate the factors that induce early articular cartilage degeneration of the hip joints that are exposed to reduced dynamic loads arising from hip dislocation , we created rodent models of hip dislocation by swaddling. Notably, expression of periostin (Postn) was increased in the acetabular articular cartilage of the DDH models; Postn was a candidate gene associated with early articular cartilage degeneration. We showed that early articular cartilage degeneration was suppressed in Postn-/- DDH mice. Furthermore, a microgravity environment induced the expression of Postn in chondrocytes through STAT3 signaling. Postn induced catabolic factors, interleukin-6 and matrix metalloproteinase 3, in articular chondrocytes through integrin-nuclear factor κB signaling. Additionally, interleukin-6 stimulated Postn expression through STAT3 signaling. Thus, Postn plays a critical role in early articular cartilage degeneration associated with hip dislocation.
2022-07-20 | GSE173637 | GEO
Project description:Zhuangguguanjie formulation (ZG) can provide noticeable relief from joint pain in patients suffering from knee osteoarthritis (OA). However, the underlying mechanism has not been fully described. Male C57BL/6 mice were administered either ZG or normal saline (NS) following surgical destabilization of the medial meniscus (DMM). At weeks 4, 6 and 8 (post-surgery), knee joints were harvested and assessed with Safranin-O staining. Blood serum was collected and tested. In vitro analysis was carried out to evaluate the effects of ZG on the expression of the OA-related genes. DMM mice indicated reduced cartilage destruction and lower blood serum biomarkers of OA (COMP1 and CTX-1) following ZG treatment. Moreover, the femoral condyle and tibial plateau histological scores were significantly reduced following ZG treatment of the DMM mice. ZG could markedly downregulate the expression of OA-related genes namely, ADAMTS5, MMP3 and MMP13, while it simultaneously upregulated collagen II as demonstrated by in vitro assays. Moreover, chondrocyte apoptosis was significantly decreased following ZG treatment. These results may be caused by the up-regulation of p-AKT expression levels, since the anti-apoptotic effects of ZG can be blocked by treatment with an AKT inhibitor. ZG is capable of preventing and/or reducing the progression of OA by inhibiting chondrocyte apoptosis via the p-AKT/Caspase 3 pathway.
| S-EPMC5835806 | biostudies-literature
Project description:An exact understanding of the interplay between the articulating tissues of the knee joint in relation to the osteoarthritis (OA)-related degeneration process is of considerable interest. Therefore, the aim of the present study was to characterize the biomechanical properties of mildly and severely degenerated human knee joints, including their menisci and tibial and femoral articular cartilage (AC) surfaces. A spatial biomechanical mapping of the articulating knee joint surfaces of 12 mildly and 12 severely degenerated human cadaveric knee joints was assessed using a multiaxial mechanical testing machine. To do so, indentation stress relaxation tests were combined with thickness and water content measurements at the lateral and medial menisci and the AC of the tibial plateau and femoral condyles to calculate the instantaneous modulus (IM), relaxation modulus, relaxation percentage, maximum applied force during the indentation, and the water content. With progressing joint degeneration, we found an increase in the lateral and the medial meniscal instantaneous moduli (p < 0.02), relaxation moduli (p < 0.01), and maximum applied forces (p < 0.01), while for the underlying tibial AC, the IM (p = 0.01) and maximum applied force (p < 0.01) decreased only at the medial compartment. Degeneration had no influence on the relaxation percentage of the soft tissues. While the water content of the menisci did not change with progressing degeneration, the severely degenerated tibial AC contained more water (p < 0.04) compared to the mildly degenerated tibial cartilage. The results of this study indicate that degeneration-related (bio-)mechanical changes seem likely to be first detectable in the menisci before the articular knee joint cartilage is affected. Should these findings be further reinforced by structural and imaging analyses, the treatment and diagnostic paradigms of OA might be modified, focusing on the early detection of meniscal degeneration and its respective treatment, with the final aim to delay osteoarthritis onset.
| S-EPMC8134692 | biostudies-literature
Project description:Osteoarthritis is a debilitating disease that results in pain and joint stiffness. Currently, steroidal and nonsteroidal anti-inflammatory drugs and supplements aimed at restoring lubrication to the affected joint are the most successful with respect to improving patient comfort. Due to the success in lubricating therapies, there exists a keen interest to develop better therapies that mimic how lubrication occurs naturally in the joint. Here we describe the results obtained using a chondroitin sulfate chain to which is conjugated peptides that bind to either hyaluronic acid (found in high concentrations in the synovial fluid) or collagen type II (present on the cartilage surface). Our study investigates the effect of binding to the cartilage surface and interacting with hyaluronic acid on lubrication at the cartilage surface. The results described here suggest that binding to the cartilage surface is critical to supporting lubrication and did not require the addition of hyaluronic acid to reduce friction.
| S-EPMC8253085 | biostudies-literature
Project description:Symptomatic osteoarthritic lesions span large regions of joint surfaces and the ability to engineer cartilage constructs at clinically relevant sizes would be highly desirable. We previously demonstrated that nutrient transport limitations can be mitigated by the introduction of channels in 10 mm diameter cartilage constructs. In this study, we scaled up our previous system to cast and cultivate 40 mm diameter constructs (2.3 mm overall thickness); 4 mm diameter and channeled 10 mm diameter constructs were studied for comparison. Furthermore, to assess whether prior results using primary bovine cells are applicable for passaged cells-a more clinically realistic scenario-we cast constructs of each size with primary or twice-passaged cells. Constructs were assessed mechanically for equilibrium compressive Young's modulus (EY), dynamic modulus at 0.01 Hz (G*), and friction coefficient (μ); they were also assessed biochemically, histologically, and immunohistochemically for glycosaminoglycan (GAG) and collagen contents. By maintaining open channels, we successfully cultured robust constructs the size of entire human articular cartilage layers (growing to ∼52 mm in diameter, 4 mm thick, mass of 8 g by day 56), representing a 100-fold increase in scale over our 4 mm diameter constructs, without compromising their functional properties. Large constructs reached EY of up to 623 kPa and GAG contents up to 8.9%/ww (% of wet weight), both within native cartilage ranges, had G* >2 MPa, and up to 3.5%/ww collagen. Constructs also exhibited some of the lowest μ reported for engineered cartilage (0.06-0.11). Passaged cells produced tissue of lower quality, but still exhibited native EY and GAG content, similar to their smaller controls. The constructs produced in this study are, to our knowledge, the largest engineered cartilage constructs to date which possess native EY and GAG, and are a testament to the effectiveness of nutrient channels in overcoming transport limitations in cartilage tissue engineering.
| S-EPMC5312614 | biostudies-literature