Different Stages Of Osteoarthritis Research Articles

Site-specific elastic and viscoelastic biomechanical properties of healthy and osteoarthritic human knee joint articular cartilage

Articular cartilage exhibits site-specific biomechanical properties. However, no study has comprehensively characterized site-specific cartilage properties from the same knee joints at different stages of osteoarthritis (OA).Cylindrical osteochondral explants (n = 381) were harvested from donor-matched lateral and medial tibia, lateral and medial femur, patella, and trochlea of cadaveric knees (N = 17). Indentation test was used to measure the elastic and viscoelastic mechanical properties of the samples, and Osteoarthritis Research Society International (OARSI) grading system was used to categorize the samples into normal (OARSI 0–1), early OA (OARSI 2–3), and advanced OA (OARSI 4–5) groups.OA-related changes in cartilage mechanical properties were site-specific. In the lateral and medial tibia and trochlea sites, equilibrium, instantaneous and dynamic moduli were higher (p < 0.001) in normal tissue than in early and advanced OA tissue. In lateral and medial femur, equilibrium, instantaneous and dynamic moduli were smaller in advanced OA, but not in early OA, than in normal tissue. The phase difference (0.1–0.25 Hz) between stress and strain was significantly smaller (p < 0.05) in advanced OA than in normal tissue across all sites except medial tibia.Our results indicated that in contrast to femoral and patellar cartilage, equilibrium, instantaneous and dynamic moduli of the tibia and trochlear cartilage decreased in early OA. These may suggest that the tibia and trochlear cartilage degrades faster than the femoral and patellar cartilage. The information is relevant for developing site-specific computational models and engineered cartilage constructs.

Plasma-derived extracellular vesicle surface markers CD45, CD326 and CD56 correlate with the stage of osteoarthritis: a primary study of a novel and promising diagnostic tool of the disease

Recently, there is a growing interest in the research based on extracellular vesicles (EVs) which represent paracrine factors secreted by almost all cell types. Both, normal and pathological cells are able to release various types of EVs with different physiological properties, functions and compositions. EVs play an important role in intercellular communication, mechanism and tissue repair. Moreover, EVs could help not only in the treatment of diseases but also in their diagnostics. This work focused on the evaluation of the potential of EVs being used as biomarkers for the diagnosis of osteoarthritis (OA) based on a comparison of the composition of EVs separated from platelet-poor plasma (PPP) of healthy donors and OA patients at different stages of OA. OA is established as a complex syndrome with extensive impact on multiple tissues within the synovial joint. It is a chronic disease of musculoskeletal system that mainly affects the elderly. Depending on the use of the Kellgren–Lawrence classification system, there are four grades of OA which have a negative impact on patients' quality of life. It is very difficult to detect OA in its early stages, so it is necessary to find a new diagnostic method for its timely detection. PPP samples were prepared from whole blood. PPP-EVs were separated from 3 groups of donors—healthy control, early stage OA, end-stage OA, and their content was compared and correlated. EVs from PPP were separated by size exclusion chromatography and characterized in terms of their size, yield and purity by NTA, western blotting, ELISA and flow cytometry. Detection of surface markers expression in EVs was performed using MACSPlex approach. Inflammatory and growth factors in EVs were analysed using MAGPix technology. Our study confirmed significant differences between EVs surface markers of patients and healthy controls correlating with the age of donor (CD63, CD31 and ROR1) and stage of OA (CD45, CD326 and CD56), respectively. Circulating EVs have been under extensive investigation for their capability to predict OA pathology diagnosis as potential targets for biomarker discovery. Taken together, obtained results indicated that PPP-EVs surface markers could be used as potential biomarkers in the early diagnosis of OA.

Circulating miR-146b and miR-27b are efficient biomarkers for early diagnosis of Equidae osteoarthritis

One of the most orthopedic problems seen in the equine is osteoarthritis (OA). The present study tracks some biochemical, epigenetic, and transcriptomic factors along different stages of monoiodoacetate (MIA) induced OA in donkeys in serum and synovial fluid. The aim of the study was the detection of sensitive noninvasive early biomarkers. OA was induced by a single intra-articular injection of 25 mg of MIA into the left radiocarpal joint of nine donkeys. Serum and synovial samples were taken at zero-day and different intervals for assessment of total GAGs and CS levels as well as miR-146b, miR-27b, TRAF-6, and COL10A1 gene expression. The results showed that the total GAGs and CS levels increased in different stages of OA. The level of expression of both miR-146b and miR-27b were upregulated as OA progressed and then downregulated at late stages. TRAF-6 gene was upregulated at the late stage while synovial fluid COL10A1 was over-expressed at the early stage of OA and then decreased at the late stages (P < 0.05). In conclusion, both miR-146b and miR-27b together with COL10A1 could be used as promising noninvasive biomarkers for the very early diagnosis of OA.

Effects of Immobilization and Swimming on the Progression of Osteoarthritis in Mice

Osteoarthritis (OA) is a chronic joint disease characterized by the degeneration of articular cartilage and thickening and sclerosis of the subchondral bone. Mechanical factors play significant roles in the development and progression of OA, but it is still controversial whether exercise or rest is a more effective treatment for OA patients. In this study, we compared the effects of swimming and immobilization at different stages of OA in mice. Four weeks (the middle stage of OA) or eight weeks (the late stage of OA) after DMM (destabilization of the medial meniscus) surgery, the mice were subjected to four-week immobilization or swimming. Ink blot analysis and a beam walking test were performed to measure the gait and balance ability. Histological analysis was performed to determine the trabecular bone area, the thickness of subchondral bone, the thickness of the cartilage, the OARSI score, and the expression of MMP13 (matrix metalloproteinases) and IL-6 (interleukin). The results showed that at the middle stage of OA, both immobilization and swimming slowed down the progression of OA. Immobilization relieved OA to a certain extent by decreasing the production of regulatory factors to attenuate the degeneration of cartilage, which partly relieved the effects of DMM on gait, mainly in the hindlimb. Swimming mainly attenuated the thickening and rescued the area of subchondral bone.

Analysis of Nanomedicine Efficacy for Osteoarthritis

Osteoarthritis (OA) is a chronic disease and it causes considerable medical and socioeconomic burden. Currently, OA can be classified into different stages depending on its severity, from mild to severe, but there is no treatment focusing on a particular stage. In addition, conventional treatments suffer from drawbacks such as the poor effectiveness of physiotherapy, short‐term efficacy of medication, and invasiveness of surgery. Nanomedicine is a promising approach to improve OA treatments such as by prolonging the residence time of drugs in the joint and on‐demand drug release. Herein, the pathological development of OA and the cellular involvement in this process is reviewed and classified into three stages: early, intermediate, and advanced, according to its pathology and severity. Subsequently, nanomaterials that have been used to deliver drug cargo relevant to different stages of OA are reviewed. The impact of nanomaterial physicochemical properties, on therapeutic efficacy, is discussed. This is concluded by discussing the significance of minimum information reporting to standardize the use of nanomedicine for OA treatment and the potential of emerging methods including microneedles and DNA barcoding technology to improve the understanding of OA biology and improve clinical translation.

Associations of human femoral condyle cartilage structure and composition with viscoelastic and constituent-specific material properties at different stages of osteoarthritis

The relationships between structure and function in human knee femoral cartilage are not well-known at different stages of osteoarthritis. Thus, our aim was to characterize the depth-dependent composition and structure (proteoglycan content, collagen network organization and collagen content) of normal and osteoarthritic human femoral condyle cartilage (n = 47) and relate them to their viscoelastic and constituent-specific mechanical properties that are obtained through dynamic sinusoidal testing and fibril-reinforced poroelastic material modeling of stress-relaxation testing, respectively. We characterized the proteoglycan content using digital densitometry, collagen network organization (orientation angle and anisotropy) using polarized light microscopy and collagen content using Fourier transform infrared spectroscopy. In the superficial cartilage (0–10 % of thickness), the collagen network disorganization and proteoglycan loss were associated with the smaller initial fibril network modulus - a parameter representing the pretension of the collagen network. Furthermore, the proteoglycan loss was associated with the greater strain-dependent fibril network modulus - a measure of nonlinear mechanical behavior. The proteoglycan loss was also associated with greater cartilage viscosity at a low loading frequency (0.005 Hz), while the collagen network disorganization was associated with greater cartilage viscosity at a high loading frequency (1 Hz). Our results suggest that proteoglycan loss and collagen network disorganization reduce the pretension of the collagen network while proteoglycan degradation also increases the nonlinear mechanical behavior of the collagen network. Further, the results also highlight that proteoglycan loss and collagen disorganization increase the viscosity of femoral cartilage, but their contribution to increased viscosity occurs in completely different loading frequencies.

Assessment of functional roles and therapeutic potential of integrin receptors in osteoarthritis: A systematic review and meta-analysis of preclinical studies.

Integrins are heterodimeric transmembrane receptors that mediate a variety of biological function and plays a critical role in osteoarthritis (OA) pathogenesis, which may provide new targets for the development of OA therapies. However, the roles of integrins in different stages of OA remain elusive. This study aimed to synthesize all published preclinical evidence on the roles of integrin receptors in different stages of OA to identify the potential target for drug development in alleviating OA pathogenesis. Major electronic databases were used to identify related original articles. The methodological quality of all included studies was appraised using the SYRCLE risk of bias tool. We used the generic inverse variance with random effects model to calculate standardized mean differences (SMDs) and 95% confidence interval (CI). Seventeen studies were included in this systematic review. Integrin α5β1 activation increases the histopathological score both in early [SMD, 6.39; 95%CI (2.90, 9.87); p=0.0003] and late [SMD, 3.41; 95%CI (2.44, 4.38); p<0.00001] stage of OA. Integrin α5β1 also increased the core catabolic factors like MMP-3, IL-1β, and TNF-α. Interestingly, the inactivation of α5β1 integrin did not change the histopathological score (p=0.84). Similarly, β1 integrin notably increased histopathological score at both stages of OA [early; SMD, 7.13; 95%CI (2.01, 12.24); p=0.006]; [late; SMD, 10.25; 95%CI (5.11, 15.39); p<0.0001], and increased the MMP-13 levels. However, integrin β1 was upregulated at the early stage and downregulated at the late stage of OA. Furthermore, α2β1 integrin significantly increased histopathological score [SMD, 3.14; 95%CI (2.18, 4.10); p<0.00001] and MMP-13 [SMD, 2.24; 95%CI (0.07, 4.41); p=0.04]. Deactivating integrin α1β1 increased histopathological score in late [SMD, 1.53; 95%CI (0.80, 2.26); p<0.0001], but not in early [SMD, 0.90; 95%CI (-1.65, 3.45); p=0.49] stage of OA. This study provides evidence that α5β1, α2β1, and α1β1 integrin might be the potential target for future drug development in alleviating OA pathogenesis. Further work is required to establish our findings through activating/deactivating these receptors in different stages of OA.

CD8+ T Cells in OA Knee Joints Are Differentiated into Subsets Depending on OA Stage and Compartment

Osteoarthritis (OA) is no longer considered a purely degenerative disease. OA is defined as a disease of the entire joint, in which inflammation occurs in various joint tissues. The overall aim of this study was to analyze the presence and polarization of CD8+ T cell subsets in OA knee joints, in relation to the OA stage and compartment (synovial fluid (SF), synovial membrane (SM,) peripheral blood (PB)). A quantitative flow analysis of CD8+ T cell subsets to compare the SF, SM, PB, was performed in patients with different stages of OA (early, unicondylar and bicondylar OA). Samples of the SF, SM and PB were harvested from a total of 55 patients at the time of surgery. Early OA was confirmed by independent surgeons intraoperatively. Uni- and bicondylar OA was confirmed and graded by two plane radiographs. Samples were analyzed by flow cytometry for surface markers, and cytokines by intracellular staining (ICS). CD8+ T cells were shown to be differentiated into pro-inflammatory IFN-γ producing Tc1 and IL-17A producing Tc17, as well as anti-inflammatory IL-4 producing Tc2. All CD8+ T cell subsets (Tc1, Tc17, and Tc2) were detected in both the SM and SF. The percentage of CD8+ T cell subsets of the total CD8+ T cell population was dependent on the OA stage and compartment. Compared with the peripheral blood (PB), the proportion of CD8+IFN-γ+ Tc1 and CD8+IL-17A+ Tc17 was significantly increased in OA SF. This was confirmed in our data for both early OA and end-stage OA. In the SM samples of end-stage OA patients, the proportion of CD8+IL-17A+ Tc17 was significantly increased compared to the PB. Comparing SF and SM samples of end-stage OA patients, the proportion of CD8+IFN-γ+ Tc1 was significantly increased in SF, whereas there were no differences concerning CD8+IL-4+ Tc2 and CD8+IL-17A+ Tc17. End-stage OA samples showed a significant increase of CD8+IL-4+ Tc2 in the SM for both unicondylar and bicondylar OA compared to early OA. CD8+ T cells infiltrating the SM and SF in OA knees are differentiated into IFN-γ-, IL-17A-, and IL-4-producing CD8+ T cell subsets (Tc1, Tc17, Tc2). This differentiation depends on the OA stage and OA compartment. Further investigation of CD8+ T cell subsets and their interaction with other inflammatory cells such as CD4+ T cells and macrophages may help to identify novel therapeutic anti-inflammatory strategies for containing OA progression.

Role and Effectiveness of Intra-articular Injection of Hyaluronic Acid in the Treatment of Knee Osteoarthritis: A Systematic Review.

Osteoarthritis (OA) is a degenerative joint disease that causes persistent joint pain and stiffness of mainly the large peripheral weight-bearing joints. It is a leading cause of functional disability and poor quality of life. Various modalities of therapy are recommended by different research organizations at different stages of OA including non-pharmacological, pharmacological, and surgical interventions. Intra-articular injections of hyaluronic acid (HA) is widely used for over three decades in the treatment of OA. However controversies exist regarding its safety and efficacy, the number of injections and courses, type of preparation, duration of its effects, and combining it with other drugs or molecules. This study aimed to review the most recent data available in the published literature to address these.Electronic databases like Medline, Embase, ProQuest, and Google Scholar were searched for articles using keywords, intraarticular injections, hyaluronic acid, and osteoarthritis knee. The review was carried out as per PRISMA guidelines.Thirty-eight randomized control trials (RCTs) investigating the efficacy and safety of intra-articular injection of HA were included in the systematic review. Out of the 38 studies, 22 (57.9%) were double-blind, eight (21%) single-blind, three (7.9%) non-blind, four (10%) with simple randomization, and one (2.7%) was open-labeled. Total 5,025 patients were included in these studies. The mean age of the patients was 60.28 years and the osteoarthritis grade of the knee joint was 1 to 3. HA was studied as a test preparation in 19 (50%) while in another 19 (50%) it was studied as a control. In 24 (63.2%) studies, HA was used as high molecular weight preparation in eight (21%) as low molecular weight preparation while in six studies the information was not available. HA was used as a standalone preparation in 31 studies, in two studies it was injected with platelet-rich plasma (PRP) and with either low-level laser therapy (LLLT), triamcinolone (TA), betamethasone (CS), poly deoxyribonucleotide (PDRN) or dexamethasone (DX) in one study each. In the majority of the studies, HA was given as a single injection (52.6% studies) or weekly three injections (28.9% studies). In 13.2 %, it was given as weekly 5 injections and in 5.3% as weekly two injections.IA-HA injections have a limited role in the treatment of knee osteoarthritis in those patients who do not have sufficient pain relief with topical or oral medication and physical therapy. It is safe and effective except for minor side effects such as local pain and swelling lasting for a few days. Severe allergic reactions are extremely rare. They provide adequate pain relief and functional improvement for up to six months irrespective of a number of injections and type of preparations used. The combination formulations with corticosteroids or PRP or MSCs show better results than HA alone. Combining HA with newer molecules such as peptides or diclofenac for sustained and disease-modifying effects requires more studies in the future.

Corresponding Changes of Autophagy-Related Genes and Proteins in Different Stages of Knee Osteoarthritis: An Animal Model Study.

ObjectiveTo investigate the effect of autophagy expression levels of different weight‐bearing states and different stages of osteoarthritis in animal models, as well as the corresponding mechanisms.MethodsWe used the male Sprague–Dawley (SD) rats (12‐week‐old, SPF) to establish the OA animal models by modified Hulth method, and grouped animal models according to the length of time after surgery and different weight‐bearing areas. RT‐qPCR was carried out for detection of autophagy‐related genes such as Atg7, Atg12, P62, etc. Western blot analysis was used to detect the expression levels of corresponding autophagy‐related proteins such as LC3B, P62, etc. T test was performed for statistical analysis to compare different groups, while the differences were deemed statistically significant with P < 0.05. Transmission electron microscopy was used to observe the autophagosome to demonstrate the level of autophagy expression and the status of the chondrocytes.ResultsThe results of the RT‐qPCR testing showed that when the weight‐bearing cartilage of the 4‐week group (relatively mild) was compared with that of the 10‐week group (relatively severe), there were statistically significant differences in all the genes tested, in detail: Atg3 (P < 0.01), Atg7 (P < 0.01), Atg12 (P < 0.01), P62 (P < 0.0001). The expression of autophagy‐related mRNA in the 4‐week group is increased compared with that of the 10‐week group. As for the expression of proteins, Western blotting showed that in the comparison between the 4‐ and the 10‐week groups, statistically significant results include Atg12 (P < 0.01) in the non‐weight‐bearing area, with decreased autophagy in the 10‐week group compared with that of the 4‐week group, while expression of LC3B (P < 0.05) protein was significantly higher in the 4‐week group than in the control in the non‐weight‐bearing area. The expression of LC3B (P < 0.0001) and P62 (P < 0.05) in the 10‐week group were higher than that of the control. Transmission electron microscope showed that autophagy in the weight‐bearing area is stronger than that in the non‐weight‐bearing area, and autophagy in the 4‐week group is stronger than in the 10‐week group for the weight‐bearing area.ConclusionsThe expression of autophagy varies during different stages of osteoarthritis, in which the autophagy is stronger in the early stage of osteoarthritis, and gradually decreases with the progression of the disease. Autophagy in different weight‐bearing areas may also be different.

Functional and structural properties of human patellar articular cartilage in osteoarthritis

Changes in the fibril-reinforced poroelastic (FRPE) mechanical material parameters of human patellar cartilage at different stages of osteoarthritis (OA) are not known. Further, the patellofemoral joint loading is thought to include more sliding and shear compared to other knee joint locations, thus, the relations between structural and functional changes may differ in OA. Thus, our aim was to determine the patellar cartilage FRPE properties followed by associating them with the structure and composition. Osteochondral plugs (n = 14) were harvested from the patellae of six cadavers. Then, the FRPE material properties were determined, and those properties were associated with proteoglycan content, collagen fibril orientation angle, optical retardation (fibril parallelism), and the state of OA of the samples. The initial fibril network modulus and permeability strain-dependency factor were 72% and 63% smaller in advanced OA samples when compared to early OA samples. Further, we observed a negative association between the initial fibril network modulus and optical retardation (r = -0.537, p < 0.05). We also observed positive associations between 1) the initial permeability and optical retardation (r = 0.547, p < 0.05), and 2) the initial fibril network modulus and optical density (r = 0.670, p < 0.01).These results suggest that the reduced pretension of the collagen fibrils, as shown by the reduced initial fibril network modulus, is linked with the loss of proteoglycans and cartilage swelling in human patellofemoral OA. The characterization of these changes is important to improve the representativeness of knee joint models in tissue and cell scale.

Synovium-Synovial Fluid Axis in Osteoarthritis Pathology: A Key Regulator of the Cartilage Degradation Process.

Failure of conventional anti-inflammatory therapies in osteoarthritis (OA) underlines the insufficient knowledge about inflammatory mechanisms, patterns and their relationship with cartilage degradation. Considering non-linear nature of cartilage loss in OA, a better understanding of inflammatory milieu and MMP status at different stages of OA is required to design early-stage therapies or personalized disease management. For this, an investigation based on a synovium-synovial fluid (SF) axis was planned to study OA associated changes in synovium and SF along the progressive grades of OA. Gene expressions in synovial-biopsies from different grades OA patients (N = 26) revealed a peak of IL-1β, IL-15, PGE2 and NGF in early OA (Kellgren–Lawrence (KL) grade-I and II); the highest MMP levels were found in advanced stages (KL grade-III and IV). MMPs (MMP-1, 13, 2 and 9) abundance and FALGPA activity estimated in forty SFs of progressive grades showed the maximum protein levels and activity in KL grade-II and III. In an SF challenge test, SW982 and THP1 cells were treated with progressive grade SFs to study the dynamics of MMPs modulation in inflammatory microenvironment; the test yielded a result pattern, which matched with FALGPA and the protein-levels estimation. Inflammatory mediators in SFs served as steering factor for MMP up-regulation. A correlation-matrix of IL-1β and MMPs revealed expressional negative correlation.

Subchondral bone microarchitecture and mineral density in human osteoarthritis and osteoporosis: A regional and compartmental analysis.

Osteoarthritis (OA) and osteoporosis (OP) are historically considered to be inversely correlated but there may be an overlap between the pathophysiology of the two diseases. This study aimed to investigate the subchondral bone microarchitecture and matrix mineralization, and the association between them in OA and OP in relation to the degree of cartilage degeneration. Fifty-six osteochondral plugs were collected from 16 OA femoral heads. They were graded on a regional basis according to the stages of cartilage degeneration, as evaluated by a new macroscopic and a modified microscopic grading system. Twenty-one plugs were collected from seven femoral heads with OP. Plugs were scanned by microcomputed tomography and the microarchitectural and mineral properties were obtained for both subchondral plate and trabecular bone. Microarchitecture and material and apparent densities of subchondral bone in OP were similar to regions with early cartilage degeneration but different from regions with advanced cartilage degradation in OA femoral heads. Subchondral trabecular bone was more mineralized than subchondral plate in both OP and OA, and this compartmental difference varied by severity of cartilage degradation. Furthermore, the relationship among trabecular bone volume fraction, tissue mineral density, and apparent bone density was similar in OP and different stages of OA. Subchondral bone microarchitecture and mineral properties in OP are different from OA in a regionalized manner in relation to stages of cartilage degeneration. Both regional and compartmental differences at structural, material, and cellular levels need to be studied to understand the transition of OA subchondral bone from being osteoporotic to sclerotic.

Convolutional neuronal networks combined with X-ray phase-contrast imaging for a fast and observer-independent discrimination of cartilage and liver diseases stages

We applied transfer learning using Convolutional Neuronal Networks to high resolution X-ray phase contrast computed tomography datasets and tested the potential of the systems to accurately classify Computed Tomography images of different stages of two diseases, i.e. osteoarthritis and liver fibrosis. The purpose is to identify a time-effective and observer-independent methodology to identify pathological conditions. Propagation-based X-ray phase contrast imaging WAS used with polychromatic X-rays to obtain a 3D visualization of 4 human cartilage plugs and 6 rat liver samples with a voxel size of 0.7 × 0.7 × 0.7 µm3 and 2.2 × 2.2 × 2.2 µm3, respectively. Images with a size of 224 × 224 pixels are used to train three pre-trained convolutional neuronal networks for data classification, which are the VGG16, the Inception V3, and the Xception networks. We evaluated the performance of the three systems in terms of classification accuracy and studied the effect of the variation of the number of inputs, training images and of iterations. The VGG16 network provides the highest classification accuracy when the training and the validation-test of the network are performed using data from the same samples for both the cartilage (99.8%) and the liver (95.5%) datasets. The Inception V3 and Xception networks achieve an accuracy of 84.7% (43.1%) and of 72.6% (53.7%), respectively, for the cartilage (liver) images. By using data from different samples for the training and validation-test processes, the Xception network provided the highest test accuracy for the cartilage dataset (75.7%), while for the liver dataset the VGG16 network gave the best results (75.4%). By using convolutional neuronal networks we show that it is possible to classify large datasets of biomedical images in less than 25 min on a 8 CPU processor machine providing a precise, robust, fast and observer-independent method for the discrimination/classification of different stages of osteoarthritis and liver diseases.

An ex vivo human osteochondral culture model.

To reduce animal experimentation and to overcome translational issues in cartilage tissue engineering, there is a need to develop an ex vivo human tissue‐based approach. This study aims to demonstrate that a human osteochondral explant at different stages of osteoarthritis (OA) can be kept in long‐term culture while preserving its viability and composition. Osteochondral explants with either a smooth or fibrillated cartilage surface, representing different OA stages, were harvested from fresh human tibial plateaus. Explants were cultured for 2 or 4 weeks in a double‐chamber culture platform. The biochemical content of the cartilage of cultured explants did not significantly change over a period of 4 weeks and these findings were supported by histology. Chondrocytes mostly preserved their metabolic activity during culture and active bone and marrow were found in the periphery of the explants, while metabolic activity was decreased in the bone core in cultured explants compared to fresh explants. In fibrillated explants, chondrocyte viability decreased in the periphery of the sample in cultured groups compared to fresh explants (fresh, 94 ± 6%; cultured, 64% ± 17%, 2 weeks, and 69% ± 17%, 4 weeks; P < .05). Although biochemical and histological results did not show changes within the cartilage tissue, the viability of the explants should be carefully controlled for each specific use. This system provides an alternative to explore drug treatment and implant performance under more controlled experimental conditions than possible in vivo, in combination with clinically relevant human osteochondral tissue.

Structure\u2013Function Relationships of Healthy and Osteoarthritic Human Tibial Cartilage: Experimental and Numerical Investigation

Relationships between composition, structure and constituent-specific functional properties of human articular cartilage at different stages of osteoarthritis (OA) are poorly known. We established these relationships by comparison of elastic, viscoelastic and fibril-reinforced poroelastic mechanical properties with microscopic and spectroscopic analysis of structure and composition of healthy and osteoarthritic human tibial cartilage (n = 27). At a low frequency (0.005 Hz), proteoglycan content correlated negatively and collagen content correlated positively with the phase difference (i.e. tissue viscosity). At a high-frequency regime (> 0.05 Hz), proteoglycan content correlated negatively and collagen orientation angle correlated positively with the phase difference. Proteoglycans were lost in the early and advanced OA groups compared to the healthy group, while the superficial collagen orientation angle was greater only in the advanced OA group compared to the healthy group. Simultaneously, the initial fibril network modulus (fibril pretension) was smaller in the early and advanced OA groups compared to the healthy group. These findings suggest different mechanisms contribute to cartilage viscosity in low and high frequencies, and that the loss of superficial collagen pretension during early OA is due to lower tissue swelling (PG loss), while in advanced OA, both collagen disorganization and lower swelling modulate the collagen fibril pretension.

Detecting human articular cartilage degeneration in its early stage with polarization-sensitive optical coherence tomography.

Detecting articular cartilage (AC) degeneration in its early stage plays a critical role in the diagnosis and treatment of osteoarthritis (OA). Polarization-sensitive optical coherence tomography (PS-OCT) is sensitive to the alteration and disruption of collagen organization that happens during OA progression. This study proposes an effective OA evaluating method based on PS-OCT imaging. A slope-based analysis is applied on the phase retardation images to segment articular cartilage into three zones along the depth direction. The boundaries and birefringence coefficients (BRCs) of each zone are quantified. Two parameters, namely phase homogeneity index (PHI) and zonal distinguishability (Dz), are further developed to quantify the fluctuation within each zone and the zone-to-zone variation of the tissue birefringence properties. The PS-OCT based evaluating method then combines PHI and Dz to provide a G PS score for the severity of OA. The proposed method is applied to human hip joint samples and the results are compared with the grading by histology images. The G PS score shows very strong statistical significance in differentiating different stages of OA. Compared to using the BRC of each zone or a single BRC for the entire depth, the G PS score shows great improvement in differentiating early-stage OA. The proposed method is shown to have great potential to be developed as a clinical tool for detecting OA.

Plateletten Zengin Plazma Uygulama Sıklığının Erken Evre Diz Osteoartriti Üzerine Etkisi

ABSTRACT Introduction: Platelet rich plasma (PRP) revealed quite satisfying results for early knee osteoarthritis (OA) especially in younger ages by decreasing pain and improving function and quality of life. However, what becomes the ideal dose and how often it should be performed, the effectiveness of intra-articular PRP application in different stages of OA are the main topics discussed. There are few studies in the literature comparing the efficacy of PRP with the administration dose. The primary aim of this study was to compare the efficacy of different doses of PRP in primary knee OA and to determine the ideal treatment modality. Material and methods: 174 patients who met the criteria were evaluated retrospectively between January 2016 and April 2017. The patients were divided into 3 groups according to doses. Western Ontario and McMaster University Arthritis Index (WOMAC) scores, International Knee Documentation Committee (IKDC) scores and 100 mm Visual Analogue Scale (100 mm VAS) scores were evaluated before treatment, 6 months and 12 months after treatment. Satisfaction status and treatment-related complications were examined at 12 months after treatment. Results: At the end of the follow-up, a significant improvement was observed in all three groups compared to the pre-treatment values. (p &amp;lt;0.05). Significant improvement was observed in pain scores (p &amp;lt;0.001) and functional scores (p &amp;lt;0.001) in all three injection groups. No significant difference was observed between twice or thrice applications (p &amp;gt;0.05). The clinical and functional results of one application was significantly lower than the other groups (p &amp;lt;0.05). Conclusion: We think that single dose therapy is less sufficient in effect, thus the appropriate method of treatment is at least 2 doses of PRP.

Thermal analysis of synovial fluids in different stages of osteoarthritis and after bacterial infections

The analysis of synovial fluid is an important method in diagnosing and handling septic arthritis. To achieve a quick diagnosis could be a great advantage in the therapy. The differential scanning calorimetry (DSC) proved to be a useful technique in the differential diagnosis of tumors using blood plasma or sera. The aim of this paper is to show up some characteristic thermal parameters in the diagnosis of different grades of arthritis, which are in good agreement with the severity of disease checked by conventional X-ray supported grading. To follow the effect of different bacterial strains, the synovial fluids were inoculated by three types of bacterial strains (with 103–105 CFU mL−1 concentrations) at 37 °C and stored trough 24 h. After that, they were denatured in 20–90 °C temperature range with 0.3 K min−1 scanning rate. The change in the maximum denaturation temperature (Tm) and calorimetric enthalpy (∆H) monitored the severity of sepsis and depended on the type of bacteria. The proliferation characteristics of bacteria should be strain specific. The synovial fluid samples inoculated with the most frequently occurring bacteria were monitored in isotherm mode (isoperibol calorimeter) at 37 °C up to the end of the proliferation. The isoperibolic scans clearly demonstrated specific, concentration-dependent representative curves in case of each bacterium (duration of proliferation, maximum of proliferation rates, etc.). Therefore, thermal analysis of human synovial fluid samples by DSC or isoperibolic calorimetry could be a useful tool in the staging of osteoarthritis and the diagnostics of septic arthritis.

Visualization of Cartilage from Knee Joint Magnetic Resonance Images and Quantitative Assessment to Study the Effect of Age, Gender and Body Mass Index (BMI) in Progressive Osteoarthritis (OA).

Osteoarthritis (OA) is a degenerative disease of joint cartilage affecting the elderly people around the world. Visualization and quantification of cartilage is very much essential for the assessment of OA and rehabilitation of the affected people. Magnetic Resonance Imaging (MRI) is the most widely used imaging modality in the treatment of knee joint diseases. But there are many challenges in proper visualization and quantification of articular cartilage using MRI. Volume rendering and 3D visualization can provide an overview of anatomy and disease condition of knee joint. In this work, cartilage is segmented from knee joint MRI, visualized in 3D using Volume of Interest (VOI) approach. Visualization of cartilage helps in the assessment of cartilage degradation in diseased knee joints. Cartilage thickness and volume were quantified using image processing techniques in OA affected knee joints. Statistical analysis is carried out on processed data set consisting of 110 of knee joints which include male (56) and female (54) of normal (22) and different stages of OA (88). The differences in thickness and volume of cartilage were observed in cartilage in groups based on age, gender and BMI in normal and progressive OA knee joints. The results show that size and volume of cartilage are found to be significantly low in OA as compared to normal knee joints. The cartilage thickness and volume is significantly low for people with age 50 years and above and Body Mass Index (BMI) equal and greater than 25. Cartilage volume correlates with the progression of the disease and can be used for the evaluation of the response to therapies. The developed methods can be used as helping tool in the assessment of cartilage degradation in OA affected knee joint patients and treatment planning.