Understanding Of Osteoarthritis Research Articles

Systems analysis of miR-199a/b-5p and multiple miR-199a/b-5p targets during chondrogenesis

Changes in chondrocyte gene expression can contribute to the development of osteoarthritis (OA), and so recognition of the regulative processes during chondrogenesis can lead to a better understanding of OA. microRNAs (miRNAs) are key regulators of gene expression in chondrocytes/OA, and we have used a combined experimental, bioinformatic, and systems biology approach to explore the multiple miRNA–mRNA interactions that regulate chondrogenesis. A longitudinal chondrogenesis bioinformatic analysis identified paralogues miR-199a-5p and miR-199b-5p as pro-chondrogenic regulators. Experimental work in human cells demonstrated alteration of miR-199a-5p or miR-199b-5p expression led to significant inverse modulation of key chondrogenic genes and extracellular matrix production. miR-199a/b-5p targets FZD6, ITGA3 and CAV1 were identified by inhibition experiments and verified as direct targets by luciferase assay. The experimental work was used to generate and parameterise a multi-miRNA 14-day chondrogenesis kinetic model to be used as a repository for the experimental work and as a resource for further investigation of this system. This is the first multi-miRNA model of a chondrogenesis-based system, and highlights the complex relationships between regulatory miRNAs, and their target mRNAs.

PERSONALIZED STATISTICAL MODELLING OF MENISCAL KINEMATICS

Intra-articular cartilage pressure distribution in the knee joint is critical in the understanding of osteoarthritis. Combining personalized statistical modeling of the morphological characteristics with discrete element modeling enables patient-specific predictions of the pressure on the tibial plateau. However, modeling of the meniscus during gait is complicated by the dynamic nature of the structure. Nevertheless, the position of the meniscus has a substantial impact on intra-articular stress distribution. Therefore, the focus of this presentation will be on how modeling of meniscal movement during knee flexion improves insight in general meniscal kinematics for the use in tibiofemoral stress distribution calculations.

Level of Inflammation and its Association with Pain, Physical Functioning and KL-Grade in Patients With Knee Osteoarthritis

Background: Knee osteoarthritis (OA), also known as degenerative arthritis, causes a progressive loss of articular cartilage. In recent years, there has been a shift in the understanding of OA from a “wear and tear” disease to an “inflammatory” condition. Aims and Objectives: The objective of this study was to assess the level of inflammation and to evaluate the relationship between inflammation, pain, physical functioning, and Kellgren Lawrence (KL)-grade in patients with knee OA. Materials and Methods: Sixty patients with radiographic evidence of knee OA (KL Grade I/II/III) were cross-sectionally analyzed. Data about their anthropometry, inflammatory markers high-sensitivity C-reactive protein (hsCRP), erythrocyte sedimentation rate-(ESR), pain, and physical functioning were collected. Results: The mean hsCRP among the patient population was 4.6 ± 4.0 mg/L and the mean ESR was 40.4 ± 21.8 mm/h. There was a strong significant association of visual analog scale (VAS) pain score with hsCRP (r = 0.353; P = 0.005) and ESR (r = 0.269; P = 0.036). There was a strong significant association of Western Ontario and McMaster Universities OA Index score with hsCRP (r = 0.415; P = 0.001) and ESR (r = 0.413, P = 0.001). However, there was no significant difference in hsCRP or ESR when classified according to KL-grade (P > 0.05). Conclusion: The level of inflammation is high in knee OA patients. Inflammation is significantly associated with pain intensity and physical functioning in knee OA patients. However, there is no significant difference in hsCRP, ESR, and VAS when classified according to KL-grade. This emphasizes the need to study inflammatory markers in addition to radiographic evidence for informed clinical decision-making.

Identifying multivariate disease trajectories and potential phenotypes of early knee osteoarthritis in the CHECK cohort.

To gain better understanding of osteoarthritis (OA) heterogeneity and its predictors for distinguishing OA phenotypes. This could provide the opportunity to tailor prevention and treatment strategies and thus improve care. Ten year follow-up data from CHECK (1002 early-OA subjects with first general practitioner visit for complaints ≤6 months before inclusion) was used. Data were collected on WOMAC (pain, function, stiffness), quantitative radiographic tibiofemoral (TF) OA characteristics, and semi-quantitative radiographic patellofemoral (PF) OA characteristics. Using functional data analysis, distinctive sets of trajectories were identified for WOMAC, TF and PF characteristics, based on model fit and clinical interpretation. The probabilities of knee membership to each trajectory were used in hierarchical cluster analyses to derive knee OA phenotypes. The number and composition of potential phenotypes was selected again based on model fit (silhouette score) and clinical interpretation. Five trajectories representing different constant levels or changing WOMAC scores were identified. For TF and PF OA, eight and six trajectories respectively were identified based on (changes in) joint space narrowing, osteophytes and sclerosis. Combining the probabilities of knees belonging to these different trajectories resulted in six clusters ('phenotypes') of knees with different degrees of functional (WOMAC) and radiographic (PF) parameters; TF parameters were found not to significantly contribute to clustering. Including baseline characteristics as well resulted in eight clusters of knees, dominated by sex, menopausal status and WOMAC scores, with only limited contribution of PF features. Several stable and progressive trajectories of OA symptoms and radiographic features were identified, resulting in phenotypes with relatively independent symptomatic and radiographic features. Sex and menopausal status may be especially important when phenotyping knee OA patients, while radiographic features contributed less. Possible phenotypes were identified that, after validation, could aid personalized treatments and patients selection.

Remodeling Osteoarthritic Articular Cartilage under Hypoxic Conditions.

Osteoarthritis (OA) is one of the leading joint diseases induced by abnormalities or inflammation in the synovial membrane and articular cartilage, causing severe pain and disability. Along with the cartilage malfunction, imbalanced oxygen uptake occurs, changing chondrocytes into type I collagen- and type X collagen-producing dedifferentiated cells, contributing to OA progression. However, mounting evidence suggests treating OA by inducing a hypoxic environment in the articular cartilage, targeting the inhibition of several OA-related pathways to bring chondrocytes into a normal state. This review discusses the implications of OA-diseased articular cartilage on chondrocyte phenotypes and turnover and debates the hypoxic mechanism of action. Furthermore, this review highlights the new understanding of OA, provided by tissue engineering and a regenerative medicine experimental design, modeling the disease into diverse 2D and 3D structures and investigating hypoxia and hypoxia-inducing biomolecules and potential cell therapies. This review also reports the mechanism of hypoxic regulation and highlights the importance of activating and stabilizing the hypoxia-inducible factor and related molecules to protect chondrocytes from mitochondrial dysfunction and apoptosis occurring under the influence of OA.

Concurrent validity and reliability of a semi-automated approach to measuring the magnetic resonance imaging morphology of the knee joint in active youth.

Post-traumatic knee osteoarthritis is attributed to alterations in joint morphology, alignment, and biomechanics triggered by injury. While magnetic resonance (MR) imaging-based measures of joint morphology and alignment are relevant to understanding osteoarthritis risk, time consuming manual data extraction and measurement limit the number of outcomes that can be considered and deter widespread use. This paper describes the development and evaluation of a semi-automated software for measuring tibiofemoral and patellofemoral joint architecture using MR images from youth with and without a previous sport-related knee injury. After prompting users to identify and select key anatomical landmarks, the software can calculate 37 (14 tibiofemoral, 23 patellofemoral) relevant geometric features (morphology and alignment) based on established methods. To assess validity and reliability, 11 common geometric features were calculated from the knee MR images (proton density and proton density fat saturation sequences; 1.5 T) of 76 individuals with a 3-10-year history of youth sport-related knee injury and 76 uninjured controls. Spearman's or Pearson's correlation coefficients (95% CI) and Bland-Altman plots were used to assess the concurrent validity of the semi-automated software (novice rater) versus expert manual measurements, while intra-class correlation coefficients (ICC2,1; 95%CI), standard error of measurement (95%CI), 95% minimal detectable change, and Bland-Altman plots were used to assess the inter-rater reliability of the semi-automated software (novice vs resident radiologist rater). Correlation coefficients ranged between 0.89 (0.84, 0.92; Lateral Trochlear Inclination) and 0.97 (0.96, 0.98; Patellar Tilt Angle). ICC estimates ranged between 0.79 (0.63, 0.88; Lateral Patellar Tilt Angle) and 0.98 (0.95, 0.99; Bisect Offset). Bland-Altman plots did not reveal systematic bias. These measurement properties estimates are equal, if not better than previously reported methods suggesting that this novel semi-automated software is an accurate, reliable, and efficient alternative method for measuring large numbers of geometric features of the tibiofemoral and patellofemoral joints from MR studies.

Emerging and New Treatment Options for Knee Osteoarthritis.

Osteoarthritis (OA) is the most prevalent type of arthritis worldwide, resulting in pain and often chronic disability and a significant burden on healthcare systems globally. Non-steroidal anti-inflammatory drugs (NSAIDs), analgesics, intra-articular corticosteroid injections are of little value in the long term, and opioids may have ominous consequences. Radiotherapy of knee OA has no added value. Physical therapy, exercises, weight loss, and lifestyle modifications may give pain relief, improve physical functioning and quality of life. However, none of them has articular cartilage regenerating potential. Due to a better understanding of osteoarthritis, innovative new treatment options have been developed. In this narrative review, we focus on emerging OA knee treatments, relieving symptoms, and regenerating damaged articular cartilage that includes intra-articular human serum albumin, conventional disease-modifying anti-rheumatic drugs (DMARDs), metformin, lipid-lowering agents (statin), nerve growth factors antagonists, bone morphogenetic protein, fibroblast growth factors, Platelet-Rich Plasma (PRP), Mesenchymal Stem Cells (MSC), exosomes, interleukin-1 blockers, gene-based therapy, and bisphosphonate.

Understanding the management of osteoarthritis: A qualitative study of GPs and orthopaedic surgeons in Tasmania, Australia

ObjectiveUsing a qualitative design this study aimed to 1) explore the attitudes towards and understanding of osteoarthritis (OA) held by Tasmanian general practitioners (GPs) and orthopaedic surgeons, 2) gain a deeper understanding of conservative and surgical management and 3) identify key barriers and challenges. DesignPurposive sampling was used to recruit 17 ​GPs and 10 surgeons from Tasmania, Australia. Semi-structured interviews were audio-recorded, transcribed, coded, and thematically analysed to document understanding of OA, management and treatment decision making. ResultsGPs and surgeons had a shared understanding of the cause and management of OA which aligned well with evidence-based best practice. Most GPs acknowledged that severity of disease on an X-Ray does not correlate well with symptoms, although some GPs reported always using imaging to support their diagnosis. Conservative management was highly supported by all interviewees, focussing on exercise and/or physiotherapy. Key treatment barriers included managing poor patient understanding of OA, unrealistic expectations for treatment, lack of patient motivation and scepticism towards exercise, and cost and accessibility of conservative treatment options. Surgery was considered a suitable option when conservative management options had been exhausted. ConclusionThis study uniquely interviewed GPs and surgeons from the same population, capturing two crucial areas of OA management. Some key barriers to treatment were identified and options for improving treatment include creating opportunities for increased patient education about OA, enhanced accessibility to OA conservative management programs along with improved reimbursement models supporting conservative management as first-line OA treatment.

Identifying trajectories of T2 relaxation time over age in the medial tibiofemoral cartilage in participants with pre-radiographic knee osteoarthritis

Identifying trajectories of T2 relaxation time over age in the medial tibiofemoral cartilage in participants with pre-radiographic knee osteoarthritis

Metabolism and global protein glycosylation are differentially expressed in healthy and osteoarthritic equine carpal synovial fluid.

Carpal osteochondral fragmentation and subsequent post-traumatic osteoarthritis (PTOA) are leading causes of wastage in the equine athlete. Identification of synovial fluid biomarkers could contribute to the diagnosis and understanding of osteoarthritis (OA) pathophysiology. The aim of this study was to identify differentially expressed metabolic and glycosylation pathways in synovial fluid from healthy horses and horses with naturally occurring carpal OA. Cross-sectional, in vivo metabolomics and glycomics study. In cohort 1, carpal synovial fluid (n=12 horses; n=6 healthy, n=6 OA) was analysed using high-resolution liquid chromatography mass spectrometry (LC-MS). In cohort 2 (n=40 horses; n=20 healthy, n=20 OA), carpal synovial fluid was analysed using lectin microarrays and a lubricin sandwich ELISA. Metabolomic analysis identified >4900 LC-MS features of which 84 identifiable metabolites were differentially expressed (P<.05) between healthy and OA joints, including key pathways related to inflammation (histidine and tryptophan metabolism), oxidative stress (arginine biosynthesis) and collagen metabolism (lysine metabolism). Principle Component Analysis and Partial Least Squares Discriminant Analysis demonstrated separation between healthy and OA synovial fluid. Lectin microarrays identified distinct glycosylation patterns between healthy and OA synovial fluid, including increased Core 1/Core 3 O-glycosylation, increased α-2,3 sialylation and decreased α-1,2 fucosylation in OA. O-glycans predominated over N-glycans in all synovial fluid samples, and synovial fluid lubricin was increased in OA joints as compared to controls. The sample size in cohort 1 was limited, and there is inherent variation in severity and duration of joint injury in naturally occurring OA. However, LC-MS identified up to 5000 unique features. These data suggest new potential diagnostic and therapeutic targets for equine OA. Future targeted metabolomic and glycomic studies should be performed to verify these results. Lectin microarrays could be investigated as a potential screening tool for the diagnosis and therapeutic monitoring of equine OA.

Multimodal approach to intraarticular drug delivery in knee osteoarthritis.

The expectations from any future disease-modifying treatment for knee osteoarthritis (KOA) are extremely high as it has to impact the joint as a whole leading to favorable alterations of diverse tissues and functions. In this light, targeting the knee only from the inside may not be biologically justified for the management of a whole joint disease such as KOA. Our hypothesis to test is whether any injectable therapeutic intervention alone can lead to disease modification of KOA which is viewed in the complexity of the modern concept of osteoarthritis (OA) as a whole joint disease. Therefore, we aimed at analyzing the intraarticular route to the KOA patient in an attempt to unveil its "biological" constraints. A comprehensive search through databases was carried out using specific keywords to add objectivity to the main messages. The literature analysis has shown that "cutting-edge" intraarticular therapies may offer a key to non-invasive symptomatic relief. Changing the course of KOA, however, may necessitate a multimodal approach towards the knee joint including a combination of intraarticular injections with interventions on multiple levels. Importantly, our understanding of OA has evolved redefining the concept of the disease, being in interaction with the human body as a whole. Any future conservative disease-modifying treatment of KOA should aim at a multimodal, holistic approach towards the knee joint including but not limited only to intraarticular injections. A combination with other interventions should be further researched.

MicroRNAs in Synovial Pathology Associated With Osteoarthritis.

Osteoarthritis (OA) is the most common type of arthritis, a disease that affects the entire joint. The relative involvement of each tissue, and their interactions, add to the complexity of OA, hampering our understanding of the underlying molecular mechanisms, and the generation of a disease modifying therapy. The synovium is essential in maintaining joint homeostasis, and pathologies associated with the synovium contribute to joint destruction, pain and stiffness in OA. MicroRNAs (miRNAs) are post-transcriptional regulators dysregulated in OA tissues including the synovium. MiRNAs are important contributors to OA synovial changes that have the potential to improve our understanding of OA and to act as novel therapeutic targets. The purpose of this review is to summarize and integrate current published literature investigating the roles that miRNAs play in OA-related synovial pathologies including inflammation, matrix deposition and cell proliferation.

Understanding osteoarthritis pathogenesis: a multiomics system-based approach.

Osteoarthritis is a heterogeneous, multifactorial condition regulated by complex biological interactions at multiple levels. Comprehensive understanding of these regulatory interactions is required to develop feasible advances to improve patient outcomes. Improvements in technology have made extensive genomic, transcriptomic, epigenomic, proteomic, and metabolomic profiling possible. This review summarizes findings over the past 20 months related to omics technologies in osteoarthritis and examines how using a multiomics approach is necessary for advancing our understanding of osteoarthritis as a disease to improve precision osteoarthritis treatments. Using the search terms 'genomics' or 'transcriptomics' or 'epigenomics' or 'proteomics' or 'metabolomics' and 'osteoarthritis' from January 1, 2018 to August 31, 2019, we identified advances in omics approaches applied to osteoarthritis. Trends include untargeted whole genome, transcriptome, proteome, and metabolome analyses leading to identification of novel molecular signatures, cell subpopulations and multiomics validation approaches. To address the complexity of osteoarthritis, integration of multitissue analyses by multiomics approaches with the inclusion of longitudinal clinical data is necessary for a comprehensive understanding of the disease process, and for appropriate development of efficacious diagnostics, prognostics, and biotherapeutics.

Osteoarthritis: epidemiology, classification, risk factors, and progression, clinical presentation, diagnosis, and treatment

For the first time, the paper presents in detail the prevalence of osteoarthritis (OA) and considers the predictors of disease development and progression. The clinical classification of OA and its place in the ICD-10 are described. The clinical presentation of the disease is characterized in detail according to the localization of the process. It is noted that there is a change in the understanding of OA as a classic model of nociceptive pain. The paper depicts clinical, laboratory, and instrumental methods for diagnosing the disease, as well as classification and diagnostic criteria; much attention is paid to the current principles of OA therapy according to the Russian clinical recommendations and the guidelines of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) and the European League Against Rheumatism (EULAR).

Mechanosensitive MiRs regulated by anabolic and catabolic loading of human cartilage

Elucidation of whether miRs are involved in mechanotransduction pathways by which cartilage is maintained or disturbed has a particular importance in our understanding of osteoarthritis (OA) pathophysiology. The aim was to investigate whether mechanical loading influences global miR-expression in human chondrocytes and to identify mechanosensitive miRs responding to beneficial and non-beneficial loading regimes as potential to obtain valuable diagnostic or therapeutic targets to advance OA-treatment. Mature tissue-engineered human cartilage was subjected to two distinct loading regimes either stimulating or suppressing proteoglycan-synthesis, before global miR microarray analysis. Promising candidate miRs were selected, re-evaluated by qRT-PCR and tested for expression in human healthy vs OA cartilage samples. After anabolic loading, miR microarray profiling revealed minor changes in miR-expression while catabolic stimulation produced a significant regulation of 80 miRs with a clear separation of control and compressed samples by hierarchical clustering. Cross-testing of selected miRs revealed that miR-221, miR-6872-3p, miR-6723-5p were upregulated by both loading conditions while others (miR-199b-5p, miR-1229-5p, miR-1275, miR-4459, miR-6891-5p, miR-7150) responded specifically after catabolic loading. Mechanosensitivity of miR-221 correlated with pERK1/2-activation induced by both loading conditions. The miR-response to loading was transient and a constitutive deregulation of mechano-miRs in OA vs healthy articular cartilage was not observed. MiRs with broader vs narrower mechanosensitivity were discovered and the first group of mechanosensitive miRs characteristic for non-beneficial loading was defined that may shape the proteome differentially when cartilage tissue is disturbed. The findings prompt future investigations into miR-relevance for mechano-responsive pathways and the corresponding miR-target molecules.

The intricate microchannel structure of the human femoral head

Purpose: The presence of a subchondral channel-like microstructure that provides a direct link between articular cartilage (AC) and deeper trabecular bone has been confirmed in a handful of classic literature. Referred to as "defects” or "breaks", they are not yet three-dimensionally visualized or characterized, despite their potential importance in understanding osteoarthritis (OA) progression/initiation. Here, we demonstrate the intricate 3D microstructure of the subchondral bone (SCB) channels in healthy human femoral head, and their region-dependent pattern. The microchannels are quantified in terms of average number (Ch.N), thickness (Ch.Th), as well as their correlation to the subchondral bone plate, and cartilage thicknesses. Methods: Human femurs from the anatomical gift program of the Medizinische Hochschule Hannover (MHH) were kindly provided to us. They were independently graded by three orthopaedic surgeons according to the Outerbridge classification system, and subsequently, five healthy female joints were selected. 44 measuring points were systematically defined on each sample. They were the intersections of two sets of geometrical features that were drawn on the femoral heads: 1) Twelve concentric lines, each separated by a 30°-angle interval, starting from the center (C) of the femoral head and ending on the neck junction. 2) four parallel parasagittal planes, which divided the arc between the C and the neck junctions into four equally-spaced regions. The location of each set of measuring points was standardized using a template grid, taking into account the normalized size of each femoral head. Cylindrical specimens (n=220, D=2.00 mm) were then drilled out from each sample and scanned using a high-definition micro-CT system (μCT 50, SCANCO Medical AG, Switzerland; voxel size=1.2 μm, source voltage=90 kVp, intensity=88 μA). The SCB channels were segmented and analyzed using appropriate evaluation scripts and threshold setting. 5-m thick sagittal sections of hip joint were cut and processed for toluidine blue and hematoxylin and eosin (H&E) staining. Sections were also incubated with primary antibodies against CD31 (ab28364, Abcam, 1:100), von Willebrand Factor (vWF, Dako, 1:200), calcitonin receptor (ab11042, Abcam, 1:75), and collagen type I (ab34710, Abcam, 1:200), and then processed for immunohistochemical staining using standard protocols. Statistical evaluation was carried out using SPSS package (IBM SPSS, version 25.0). Results: The data were categorized into three groups based on the contact area of the femoral head with the acetabulum: load-bearing region (LBR), non-load-bearing region (NLBR), and partial contact (PC). The microchannels showed a strong region-dependent architecture. They were abundant and small (Ch.N = 34.2 ± 11.3 1/mm; Ch.Th = 26 ± 16 μm) on the LBR, perpendicularly connecting SCB's surface to deeper trabecular spacing, while scarce and relatively thick (Ch.N = 3.7 ± 1.3 1/mm; Ch.Th = 168 ± 82 μm) on the NLBR of the femoral head. The area where the femoral head and acetabulum were only partially in contact (PC) showed a combination of thick and small channels (Ch.N = 19.6 ± 7.7 1/mm; Ch.Th = 75 ± 53 μm). The mean AC thickness was positively correlated (Pearson’s r = 0.43) with the number of microchannels (LBR: 696 ± 209 μm, PC: 575 ± 162 μm, NLBR: 315 ± 124 μm). H&E staining of the subchondral zone showed that articular cartilage was occasionally extended through the calcified cartilage and marrow spaces. Likewise, immunohistochemistry results demonstrated positive expression for vWF inside microchannels, a specific marker for endothelial cells. Conclusions: Our results demonstrate that an intricate microchannel structure exists in the subchondral bone of the human femoral head. The number, width, and distribution pattern of the channels is strongly region-dependent. The positive correlation of microchannel numbers with AC thickness in healthy femurs shows that they might play a dynamic role in the nutrition of AC.

Identification of pathways and genes associated with synovitis in osteoarthritis using bioinformatics analyses

Synovitis in osteoarthritis (OA) is a very common condition. However, its underlying mechanism is still not well understood. This study aimed to explore the molecular mechanisms of synovitis in OA. The gene expression profile GSE82107 (downloaded from the Gene Expression Omnibus database) included 10 synovial tissues of the OA patients and 7 synovial tissues of healthy people. Subsequently, differentially expressed gene (DEG) analysis, GO (gene ontology) enrichment analysis, pathway analysis, pathway network analysis, and gene signal network analysis were performed using Gene-Cloud of Biotechnology Information (GCBI). A total of 1,941 DEGs consisting of 1,471 upregulated genes and 470 downregulated genes were determined. Genes such as PSMG3, LRP12 MIA-RAB4B, ETHE1, SFXN1, DAZAP1, RABEP2, and C9orf16 were significantly regulated in synovitis of OA. In particular, the MAPK signalling pathway, apoptosis, and pathways in cancer played the most important roles in the pathway network. The relationships between these pathways were also analysed. Genes such as NRAS, SPHK2, FOS, CXCR4, PLD1, GNAI2, and PLA2G4F were strongly implicated in synovitis of OA. In summary, this study indicated that several molecular mechanisms were implicated in the development and progression of synovitis in OA, thus improving our understanding of OA and offering molecular targets for future therapeutic advances.

Correlation between protein YKL-40 and ultrasonographic findings in active knee osteoarthritis.

A prospective study with fifty consecutive patients with active knee OA (diagnosed based on the American College of Rheumatology criteria for OA with radiographic confirmation) was performed. Concentrations of YKL-40 in serum and synovial fluid were measured by ELISA. US examinations - Gray scale (GS) US and Power Doppler (PD) US - of the knee was performed according to international guidelines. The suprapatellar, medial and lateral parapatellar recesses were scanned in each knee to evaluate synovial hypertrophy and vascularization. Forty women (mean age 61.50±11.33 years old) and 10 men (aged 68.50±6.60 years old) were enrolled. We found that the synovial level of the glycoprotein (237.80±104.08 ng/ml) was significantly higher compared to the serum concentration (112.83±60.61 ng/ml, p<0.001). The serum concentration in OA patients was higher comparing with age-matched healthy controls (84.19±11.39 ng/ml) (p<0.05). A statistically significant association between YKL- 40 in synovial fluid and serum levels was shown. We determined a moderately positive linear relationship between the synovial level of the glycoprotein and the serum concentration. No association between the levels of inflammatory markers - erythrocyte sedimentation rate and C-reactive protein - and YKL-40 concentrations was detected. Our study revealed a strong relationship between YKL-40 in synovial fluid and GS US and feeble with PD US. YKL-40 correlated with inflammatory activity in knee joints and neovascularization detected by US. YKL-40 is involved in the pathogenesis of OA synovitis. Evaluation of YKL-40 levels in parallel with US might provide more sensitive and reliable information for the diagnosis and understanding of OA.

An Autologous Anti-Inflammatory Protein Solution Yielded a Favorable Safety Profile and Significant Pain Relief in an Open-Label Pilot Study of Patients with Osteoarthritis.

Osteoarthritis (OA) is a progressive and degenerative disease, which may result in significant pain and decreased quality of life. Recent updates in our understanding of OA have demonstrated that it is a whole joint disease that has many similarities to an unhealed wound containing inflammatory cytokines. The nSTRIDE Autologous Protein Solution (APS) Kit is a medical device under development for the treatment of OA. The APS Kit processes a patient's own blood at the point of care to contain high concentrations of anti-inflammatory cytokines and anabolic growth factors. This study assessed the safety and treatment effects of a single intra-articular injection of APS. Eleven patients were enrolled in this study. Sufficient blood could not be drawn from one patient who was subsequently withdrawn, leaving 10 patients treated. Minor adverse events (AEs) were experienced by seven subjects (63.6%). There was one serious AE (diverticulitis) unrelated to the device or procedure. One subject experienced AEs that were judged “likely” to be procedure related (arthralgia/musculoskeletal discomfort) and all resolved within 6 days of injection. All other AEs were unrelated to the device or procedure. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain scores improved significantly over time (ANOVA, p < 0.0001, 12.0 ± 1.2 preinjection, 3.3 ± 2.9 one year postinjection, and 72.5% WOMAC pain improvement). There was significant positive correlation between white blood cell concentration in APS and improvement in WOMAC pain scores.

Unraveling the role of Calcium ions in the mechanical properties of individual collagen fibrils

Collagen, the dominating material in the extracellular matrix, provides the strength, elasticity and mechanical stability to the organisms. The mechanical property of collagen is mainly dominated by its surrounding environments. However, the variation and origin of the mechanics of collagen fibril under different concentrations of calcium ions (χCa) remains unknown. By using the atomic force microscopy based nanoindentation, the mechanics and structure of individual type II collagen fibril were first investigated under different χCa in this study. The results demonstrate that both of the mechanical and structural properties of the collagen fibril show a prominent dependence on χCa. The mechanism of χCa-dependence of the collagen fibril was attributed to the chelation between collagen molecules and the calcium ions. Given the role of calcium in the pathology of osteoarthritis, the current study may cast new light on the understanding of osteoarthritis and other soft tissue hardening related diseases in the future.