Osteoarthritis Research Research Articles

Machine Learning Approaches for the Fusion of Near-Infrared, Mid-Infrared, and Raman Data to Identify Cartilage Degradation in Human Osteochondral Plugs.

Vibrational spectroscopy methods such as mid-infrared (MIR), near-infrared (NIR), and Raman spectroscopies have been shown to have great potential for in vivo biomedical applications, such as arthroscopic evaluation of joint injuries and degeneration. Considering that these techniques provide complementary chemical information, in this study, we hypothesized that combining the MIR, NIR, and Raman data from human osteochondral samples can improve the detection of cartilage degradation. This study evaluated 272 osteochondral samples from 18 human knee joins, comprising both healthy and damaged tissue according to the reference Osteoarthritis Research Society International grading system. We established the one-block and multi-block classification models using partial least squares discriminant analysis (PLSDA), random forest, and support vector machine (SVM) algorithms. Feature modeling by principal component analysis was tested for the SVM (PCA-SVM) models. The best one-block models were built using MIR and Raman data, discriminating healthy cartilage from damaged with an accuracy of 77.5% for MIR and 77.8% for Raman using the PCA-SVM algorithm, whereas the NIR data did not perform as well achieving only 68.5% accuracy for the best model using PCA-SVM. The multi-block approach allowed an improvement with an accuracy of 81.4% for the best model by PCA-SVM. Fusing three blocks using MIR, NIR, and Raman by multi-block PLSDA significantly improved the performance of the single-block models to 79.1% correct classification. The significance was proven by statistical testing using analysis of variance. Thus, the study suggests the potential and the complementary value of the fusion of different spectroscopic techniques and provides valuable data analysis tools for the diagnostics of cartilage health.

No difference in osteoarthritis, but less graft failures after 5 years, comparing anatomic double-bundle to anatomic single-bundle ACL reconstruction.

The purpose of this study was to compare the incidence of knee osteoarthritis (OA) between the anatomic single-bundle (SB) and anatomic double-bundle (DB) anterior cruciate ligament (ACL) reconstruction technique after 5-year follow-up (FU). Secondary objectives were to compare patient-reported outcome measures (PROMs), clinical examination, activity level, functional tests and graft failures between the two groups. The study was a secondary analysis after 5-year FU of a randomized controlled trial (RCT) (Clinical Trials NCT01033188). One hundred and twenty patients between 18 and 40 years were randomized to either anatomic SB or anatomic DB reconstruction. The Kellgren-Lawrence (KL) classification grade ≥2 and the Osteoarthritis Research Society International (OARSI) atlas criteria score ≥2 were used for defining OA. Additionally, PROMs were obtained and clinical examinations of the knees were performed. Finally, the number of patients experiencing graft failure in each group was recorded. Radiographic imaging was performed in 39 patients in the SB group and in 37 patients in the DB group. Four patients (10%) in the SB group and two (5%) in the DB group developed osteoarthritis according to the KL classification (p = 0.28). Five (13%) in the SB group and three (8%) in the DB group developed osteoarthritis according to the OARSI atlas criteria (p = 0.59; difference 5.0% [95% confidence interval, CI: -0.10 to 0.20]). There were no significant differences in the PROMs, clinical examinations, activity levels, or functional tests when comparing the two groups. Of initially 62 SB patients, 14 (23%) experienced graft failure compared to 4 (7%) of the 58 DB patients (p = 0.015; difference 0.016 [95% CI: 0.03-0.29]). At 5-year FU, there were no significant differences in the incidence of OA, PROMS, or other clinical findings comparing the anatomic DB to anatomic SB ACL reconstructed patients. There were fewer graft failures among patients treated with anatomic DB ACL reconstruction. II.

Impact of Structural Severity on Outcomes in Knee Osteoarthritis: An Analysis of Data from Phase 2 and Phase 3 Lorecivivint Clinical Trials.

Developing knee osteoarthritis (OA) treatments is challenging due to assessing pain and joint structure outcomes within a highly heterogeneous disease. Lorecivivint (LOR), an intra-articular (IA) CLK/DYRK inhibitor, modulates Wnt and inflammatory pathways. This review analysis of LOR 0.07 mg trial data aims to describe the potential impact of baseline joint structure on OA pain response. Two Phase 2 and two Phase 3 trials enrolled knee OA patients with Kellgren-Lawrence (KL) Grades 2-3 and Pain Numeric Rating Scale (NRS [0-10]) ≥4 to ≤ 8 in target knee. Cumulative frequency distribution plots by KL grade summarized the percentages of patients with medial joint space width (medial JSW) < 3 mm. Osteoarthritis Research Society International Joint Space Narrowing grades and treatment responses in trials capturing Pain NRS were similarly summarized. Pain outcome changes were estimated using baseline adjusted ANCOVA. Compared with phase 2 trials, the phase 3 trials had an increased proportion of patients with baseline medial JSW < 3 mm. LOR demonstrated beneficial treatment effects vs placebo in KL 2 subgroups, which were found to have higher proportions of baseline medial JSW > 3 mm, apart from one Phase 3 trial with advanced structural knee OA. Baseline medial JSWs were heterogeneous across trials despite KL inclusion criteria. LOR demonstrated greater symptomatic improvements in patients with less structurally advanced disease, indicative of an association between OA structural damage and pain. Early treatment interventions may improve outcomes and provide insight for future OA trial inclusion criteria development. OA-02, NCT02536833; OA-04, NCT03122860; OA-10, NCT04385303; OA-11, NCT03928184.

Multi-centre Modified Delphi Exercise to Identify Candidate Items for Classifying Early-Stage Symptomatic Knee Osteoarthritis

To generate a list of candidate items potentially useful for discriminating individuals with Early-stage Symptomatic Knee Osteoarthritis (EsSKOA) from those with other conditions and from established osteoarthritis (OA), and to reduce this list based on expert consensus. We conducted a three-round online international modified Delphi exercise with OA clinicians and researchers ("OA experts"). In Round 1, participants reviewed 84 candidate items and nominated additional item(s) potentially useful for EsSKOA classification; those nominated by ≥3 participants were added. In Round 2, participants rated perceived usefulness of 108 items (1 [not at all useful] to 9 [extremely useful]). In Round 3, participants could revise their ratings after reviewing Round 2 group median and quartiles. Following Round 3, we retained items with a median usefulness score >5 and ≥33.3% of participants categorized the item as useful (7 to 9), overall and in subgroup analysis by clinician field. There were 128 participants in Round 1 and 113 (88%) completed all rounds. We retained 77 items that spanned multiple domains (demographics, symptoms, physical exam, performance-based measures, imaging, laboratory investigations, and gross inspection/arthroscopy). Highly rated items included (median usefulness score): prior knee joint injury (8), diagnosis of OA in a different joint (7), and activity-related knee pain (7). The interquartile range was most often 3. We identified 77 items that OA experts consider potentially useful for EsSKOA classification. The results highlight experts' uncertainty around item usefulness. Next, candidate items will be further assessed and reduced using data-driven and multicriteria decision analysis methods.

Ononin delays the development of osteoarthritis by down-regulating MAPK and NF-κB pathways in rat models.

Osteoarthritis (OA) is featured as cartilage loss, joint pain and loss of labor, which the inflammatory reaction may play critical roles. Ononin is an isoflavone isolating from medicinal plants and has anti-inflammatory effects. Our study investigated the anti-inflammation response of ononin on OA. Anterior cruciate ligament transection (ACLT)-induced OA operation was used to establish research model, then treated with ononin for 8 weeks. The condition of joint injury was assessed using pathological staining. The concentration of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) in serum were measured by Elisa kit. The expression of collagen II and matrix metalloproteinase 13 (MMP-13) proteins to assess cartilage metabolism level by immunohistochemistry and Western blot. We detected the expression of proteins involved in the MAPK and NF-κB signaling pathways. Finally, we used molecular docking to assess the affinity of ononin for the target proteins ERK1/2, JNK1/2, p38 and p65. Our results confirmed that ononin ameliorated cartilage impairment through histopathological analysis by improving the morphological structures and cartilage tidal lines and decreasing Osteoarthritis Research Society International (OARSI) scores in OA rats. Moreover, ononin inhibited the secretion of above factors in OA rats. Furthermore, ononin has been shown to improve cartilage content levels in OA rats. In addition, ononin inhibited the reactivity of MAPK and NF-κB pathways in OA rats. And molecular docking indicated the ligand molecules could stably bind to the proteins of above receptors. Our results demonstrated that ononin may ameliorate cartilage damage and inflammatory response in OA rats by downgrading MAPK and NF-κB pathways, thus identifying ononin as a potential novel drug to treat OA.

Advancing Osteoarthritis Treatment: The Therapeutic Potential of Mesenchymal Stem Cell-Derived Exosomes and Biomaterial Integration

Background/Objectives: Osteoarthritis (OA) is a prevalent and debilitating joint disorder characterized by progressive cartilage degradation and inflammation, for which traditional treatments offer only symptomatic relief without halting disease progression. Exosomes, cell-free vesicles derived from mesenchymal stem cells, have emerged as a promising alternative therapy owing to their regenerative and anti-inflammatory properties. Methods: This review synthesizes findings from recent studies (2017–2023) on the therapeutic potential of exosomes in OA treatment, highlighting their ability to modulate the joint microenvironment, reduce inflammation, and promote cartilage repair by delivering bioactive molecules such as cytokines, growth factors, and regulatory ribonucleic acids. Results: We explore the integration of exosomes with biomaterials, such as hydrogels and scaffolds, to enhance their delivery and therapeutic efficacy, and we address the critical challenges associated with their clinical application, including standardization of isolation and characterization methods, scalability of production, mechanistic understanding, and long-term safety. Despite these challenges, exosome-based therapies offer several advantages over traditional and cell-based treatments, including lower immunogenicity, ease of handling, and targeted delivery of therapeutic agents to damaged tissues. Conclusions: We provide an analytical perspective on the current state of exosome research in OA, emphasizing the need for standardized production methods, deeper mechanistic insights, and rigorous long-term safety assessments. Future directions should focus on optimizing delivery systems, exploring personalized medicine approaches, and conducting comparative effectiveness studies to fully realize the potential of exosome therapies for OA treatment. Addressing these gaps will be crucial for translating exosome therapies from bench to bedside and achieving a transformative impact on OA management.

Effects of platelet-rich plasma combined with exercise therapy for one year on knee osteoarthritis: retrospective cohort study

BackgroundPlatelet-rich plasma (PRP) is a promising treatment for knee osteoarthritis (OA). However, exercise therapy and activities of daily living (ADL) guidance are recommended as core treatments in the Osteoarthritis Research Society International (OARSI) guidelines. However, the effects of PRP combined with exercise therapy are not fully understood. This study aimed to clarify the effectiveness of this treatment.MethodsWe assigned patients diagnosed with knee OA and treated between January 2021 and December 2022 to groups who underwent PRP + exercise (PE), PRP (P), or exercise (E) therapy. Outcomes were evaluated using Knee Injury and Osteoarthritis Outcome Scores (KOOS) before, and 1, 3, and 12 months after treatment. Within-group comparisons according to the time of each score were statistically assessed using a one-way analysis of variance, then differences were analyzed using Bonferroni multiple comparisons p < 0.05). Treatment responses were determined using Outcome Measures in Rheumatology (OMERACT)-OARSI Responder criteria.ResultsPre-treatment KOOS did not significantly differ among the groups. Pain in the PE group improved within 1 month, symptoms, ADL, and quality of life (QOL) improved after 3, months and continued for 12 months. Pain and symptoms improved in the P group within 1 month, but ADLs and the QOL did not significantly change. Pain improved after 3 months in the E group and ADL, and QOL improved by 12 months. The response among the groups was the highest for the PE, with 50.0% at 1 and 3 months, and 65.0% at 12 months.ConclusionsTherapy with PRP immediately relieved pain, whereas exercise conferred late, but enduring effects. Combining PRP with exercise conferred synergistic advantages that persisted for up to 12 months.

Efficacy of disease-modifying osteoarthritis drugs in the treatment of osteoarthritis

Background: Osteoarthritis is the most common form of chronic inflammatory arthritis, and its prevalence is steadily increasing owing to its association with aging. Therefore, understanding and implementing appropriate treatments for osteoarthritis in clinical practice is becoming increasingly important. Additionally, there is active research on a new approach for treating osteoarthritis: disease-modifying osteoarthritis drugs (DMOADs).Current Concepts: Several global osteoarthritis treatment guidelines exist; this article introduces the guidelines of the American College of Rheumatology and Osteoarthritis Research Society International, which are among the most widely recognized. A common theme across various guidelines is that exercise and weight loss are the primary recommended treatments. As for pharmacotherapy, the top recommendations include topical nonsteroidal anti-inflammatory drugs (NSAIDs) and oral NSAIDs. Although multiple classes of drugs such as DMOADs are being actively researched to slow the progression of osteoarthritis, no drug has yet been confirmed to be clinically effective or approved for use.Discussion and Conclusion: A deeper understanding of osteoarthritis treatment can help prevent malpractice and improve patient outcomes. While current treatments focus primarily on symptom management, the development of effective DMOADs holds promise for fundamentally altering the disease course and improving joint function and quality of life.

Osteoarthritis year in review 2024: Biology

Osteoarthritis (OA) research is a fast-growing and extremely wide field, in which a substantial increase in knowledge has been achieved over the last year. It covers many different topics, however, a PubMed search using the terms 'osteoarthritis' and 'biology' resulted in only a limited number of studies that were published between April 2023 and April 2024. In order to identify OA-relevant studies that focus on mechanistic studies of biological processes at the tissue, cellular, and molecular level, the following keywords were included as search terms: tissue interactions, single cell sequencing, transcriptomics, extracellular matrix, signaling, ion channels, and pain. The final selection of publications presented in this 'year in review' was influenced by the personal preferences of the authors, and eventually three larger key themes emerged: 1) Joint tissue interactions covering meniscus, subchondral bone, fat tissue, synovium, and synovial fluid. 2) Degeneration of the cartilage extracellular matrix and generation of bioactive fragments. 3) Receptors, ion channels, signaling pathways, and cellular metabolism. Many of the studies summarized here identified novel potential targets for OA treatment, and promising results were already obtained addressing these targets in different animal models. It will be exciting to see which findings can be translated into future clinical studies and eventually lead to novel treatment approaches for human OA.

Knockdown of nuclear protein 1 delays pathological pro-gression of osteoarthritis through inhibiting chondrocyte ferroptosis.

To investigate the effect of nuclear protein 1 (Nupr1) on the pathological progression of osteoarthritis and its relationship with ferroptosis of chondrocytes. Chondrocytes of mouse knee were divided into small interfering RNA (siRNA) control group, small interfering RNA targeting Nupr1 (siNupr1) group, siRNA control+IL-1β group (siRNA control interference for 24 h followed by 10 ng/mL IL-1β) and siNupr1+IL-1β group (siNupr1 interference for 24 h followed by 10 ng/mL IL-1β). The protein and mRNA expressions of Nupr1 were detected by Western blotting and real-time RT-PCR. Cell proliferation viabilities were measured using the cell counting kit-8 method. The levels of ferrous ions were detected by FerroOrange staining. Lipid peroxidation levels were detected by C11-BODIPY-591 fluorescence imaging. The contents of malondialdehyde (MDA) and glutathione (GSH) were detected by enzyme-linked immunosorbent assay. The protein expressions of long-chain acyl-coenzyme A synthetase 4 (ACSL4), tumor protein 53 (P53), glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 gene (SLC7A11) were detected by Western blotting. The osteoarthritis model was constructed by destabilization of the medial meniscus (DMM) surgery in 7-week-old male C57BL/6J mice. The mice were randomly divided into 4 groups with 10 animals in each group: sham surgery (Sham)+adeno-associated virus serotype 5 (AAV5)-Short hairpin RNA (shRNA) control group, Sham+AAV5-shRNA targeting Nupr1 (shNupr1) group, DMM+AAV5-shRNA group, and DMM+AAV5-shNupr1 group. Hematoxylin and eosin staining and Safranin O-Fast Green staining were used to observe the morphological changes in cartilage tissue. The Osteoarthritis Research Society International (OARSI) osteoarthritis cartilage histopathology assessment system was used to evaluate the degree of cartilage degeneration in mice. The mRNA expressions of Nupr1, matrix metallopeptidase 13 (MMP13), a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5), cyclooxygenase 2 (COX2), and glutathione peroxidase 4 (GPX4) were detected by real-time RT-PCR. In vitro experiments showed that knocking down Nupr1 alleviated the decrease of chondrocyte proliferation activity induced by IL-1β, reduced iron accumulation in mouse chondrocytes, lowered the lipid peroxidation, downregulated ACLS4 and P53 protein expression and upregulated GPX4 and SLC7A11 protein expression (all P<0.01), thereby inhibiting ferroptosis in mouse chondrocytes. Meanwhile, in vivo animal experiments demonstrated that knocking down Nupr1 delayed the degeneration of articular cartilage in osteoarthritis mice, improved the OARSI score, slowed down the degradation of the extracellular matrix in osteoarthritis cartilage, and reduced the expression of the key ferroptosis regulator GPX4 (all P<0.01). Knockdown of Nupr1 can delay the pathological progression of osteoarthritis through inhibiting ferroptosis in mouse chondrocytes.

An Advanced Mechanically Active Osteoarthritis-on-Chip Model to Test Injectable Therapeutic Formulations: The SYN321 Case Study.

Current treatments for osteoarthritis (OA) often fail to address the underlying pathophysiology and may have systemic side effects, particularly associated with long-term use of non-steroidal anti-inflammatory drugs (NSAIDs). Thus, researchers are currently directing their efforts toward innovative polymer-drug combinations, such as mixtures of hyaluronic acid viscoelastic hydrogels and NSAIDs like diclofenac, to ensure sustained release of the NSAID within the joint following intra-articular injection. However, the progress of novel injectable therapies for OA is hindered by the absence of preclinical models that accurately represent the pathology of the disease. The uBeat® MultiCompress platform is here presented as a novel approach for studying anti-OA injectable therapeutics on human mechanically-damaged OA cartilage microtissues, in a physiologically relevant environment. This platform can accommodate injectable therapeutic formulations and is successfully tested with SYN321, a novel diclofenac-sodium hyaluronate conjugate under development as a treatment for knee OA. Results indicate the platform's effectiveness in evaluating therapeutic potential, showing downregulation of inflammatory markers and reduction in matrix degradation in OA cartilage micro-tissues treated with SYN321. The uBeat® MultiCompress platform thus represents a valuable tool for OA research, offering a bridge between traditional in vitro studies and potential clinical applications, with implications for future drug discovery.

Generative AI in orthopedics: an explainable deep few-shot image augmentation pipeline for plain knee radiographs and Kellgren-Lawrence grading.

Recently, deep learning medical image analysis in orthopedics has become highly active. However, progress has been restricted by the absence of large-scale and standardized ground-truth images. To the best of our knowledge, this study is the first to propose an innovative solution, namely a deep few-shot image augmentation pipeline, that addresses this challenge by synthetically generating knee radiographs for training downstream tasks, with a specific focus on knee osteoarthritis Kellgren-Lawrence (KL) grading. This study leverages a deep few-shot image augmentation pipeline to generate synthetic knee radiographs. Despite the limited availability of training samples, we demonstrate the capability of our proposed computational strategy to produce high-fidelity plain knee radiographs and use them to successfully train a KL grade classifier. Our experimental results showcase the effectiveness of the proposed computational pipeline. The generated synthetic radiographs exhibit remarkable fidelity, evidenced by the achieved average Frechet Inception Distance (FID) score of 26.33 for KL grading and 22.538 for bilateral knee radiographs. For KL grading classification, the classifier achieved a test Cohen's Kappa and accuracy of 0.451 and 0.727, respectively. Our computational strategy also resulted in a publicly and freely available imaging dataset of 86000 synthetic knee radiographs. Our approach demonstrates the capability to produce top-notch synthetic knee radiographs and use them for KL grading classification, even when working with a constrained training dataset. The results obtained emphasize the effectiveness of the pipeline in augmenting datasets for knee osteoarthritis research, opening doors for broader applications in orthopedics, medical image analysis, and AI-powered diagnosis.

Osteochondral Tissue-On-a-Chip: A Novel Model for Osteoarthritis Research.

The existing in vitro and in vivo models for studying osteoarthritis have significant limitations in replicating the complexity of joint tissues. This research aims to validate a Tissue-On-a-Chip system for osteoarthritis research. Osteochondral tissues obtained from knee replacement surgeries of patients with osteoarthritis were cultured in an Organ-On-a-Chip system. This system was designed to supply oxygen and glucose to the cartilage from the bone. The distribution of oxygen and glucose was evaluated by fluorescence using Image-iT Green Hypoxia and 2-NBDG, respectively. Cytotoxicity was measured using lactate dehydrogenase (LDH) levels in chip cultures compared to plate cultures (12 tissues per method). Glycosaminoglycans (GAGs), alkaline phosphatase (ALP), Coll2-1, and procollagen type II N-terminal propeptide (PIINP) were measured in the perfused medium of the Tissue-On-a-Chip over a period of 70 days. Fluorescence of Image-iT Green Hypoxia was observed only in the cartilage area, while 2-NBDG was distributed throughout the tissue. An increase in LDH levels was noted in the plate cultures on day 24 and in the Tissue-On-a-Chip cultures on day 63. Compared to the start of the culture, GAG content increased on day 52, while ALP showed variations. A notable increase in GAG, ALP, and Coll2-1 levels was observed on day 59. PIINP levels remained stable throughout the experiment. The validated osteochondral Tissue-On-a-Chip system can replicate the joint microenvironment, with hypoxic conditions in cartilage and normoxic conditions in bone. Tissue survival and component stability were maintained for approximately two months. This platform is a useful tool for evaluating new drugs and represents a viable alternative to animal models.

A novel Osteoarthritis scoring system to separate typical OA joint degeneration from non-typical lesions in male Sprague Dawley rats

ObjectiveTo develop a novel scoring system to characterize osteoarthritis-related degeneration distinct from spontaneous subchondral bone lesions observed in the tibia and femur of male Sprague Dawley rats. MethodKnee joints from male rats following 12 weeks of a diet-induced obesity model of osteoarthritis (OA) were assessed. OA histopathological changes (OAHC) were assessed in the knee joints. All scores were evaluated using a modified Mankin score and a modified Osteoarthritis Research Society International histological score. OAHC were divided into 3 categories: (I) Typical OA score evaluating the changes in cartilage structure, cellularity, proteoglycan depletion, and tidemark integrity, (II) A novel Non-typical OA score evaluating cartilage integrity, and the size of local thickening, fragmentation and degeneration along the tidemark and the size and severity of the subchondral bone lesion, and (III) Total OA score comprised of both, the Typical and the Non-typical scores. ResultsRats exposed to a high fat/high sucrose diet had higher Typical OA score compared to a control group (Chow). Non-typical and Total OA scores revealed no differences in the severity of the lesions between the HFS and the Chow group animals. All scoring systems had excellent intra- and inter-examiner reliability. ConclusionThe spontaneous bone lesions observed in male Sprague Dawley rats can obscure the effect of the diet-induced obesity if the classical scoring system is used to assess joint degeneration. The newly proposed scoring method provides a reliable method to distinguish classical OA joint degeneration from spontaneous Non-typical lesions occurring in these rats.

Combined exosome of adipose-derived mesenchymal stem cell and hyaluronic acid delays early osteoarthritis progression of ovine sheep model: Clinical, radiographic, macroscopic and microscopic evaluation

Background Current treatment of osteoarthritis (OA) mainly focused on treating symptoms. Exosome from Adipose-derived Mesenchymal Stem Cell (Ad-MSC) have been shown to delay degenerative process. This study aimed to investigate the clinical, radiological and histological impact of combined intra-articular (IA) hyaluronic acid (HA) and exosome Ad-MSCs in-vivo using a larger animal model with low-grade OA. Methods Eighteen male Ovies aries sheep underwent total lateral meniscectomy and conventional radiography was performed to confirm low-grade OA after 6 weeks. The sheep were divided into three groups, Group 1 (G1; n=6) received thrice exosome injections, G2 (n=6) received twice HA injection, and G3 (n=6) received both treatments with a 1-week interval after 10 days of meniscectomy. Clinical evaluations were conducted using the Clinical Lameness Score (CLS), radiographic with X-ray using OA score by Innes et al, while macroscopic evaluation by Osteoarthritis Research Society International (OARSI) scores. Results Lameness parameter scored lowest in G3 significantly (2.0±0.0 VS 2.7±0.52 VS 2.7±0.52; p=0.024) at the second month although the overall CLS score did not significantly differ at the 3rd month. The best improvement of conventional total OA radiographic score at the 3rd month compared to all groups (5.2±1.17 vs 6.3±0.82 vs 6.7±1.03; p=0.053). Macroscopic OARSI evaluation showed no difference (p=0.711). Conclusions Combined repeated exosome Ad-MSC and HA IA injection proven to delay OA progression, however longer duration of follow up is required to evaluate its long-term effect.

Assessment of whole cartilage surface damage in an osteoarthritis rat model: The Cartilage Roughness Score (CRS) utilizing microcomputed tomography

ObjectiveThis study aims to establish an accurate and robust imaging biomarker for pre-clinical osteoarthritis (OA) research, focusing on early detection of cartilage surface degeneration. MethodUsing 50 male Wistar rats, this study aims to observe Collagenase Induced Osteoarthritis (CIOA) progression through microcomputed x-ray tomography (µCT), histopathological analysis, and gait analysis. A novel parameter, Cartilage Roughness Score (CRS), was developed for assessing cartilage structural damage from µCT data and was compared with histological OARSI Cartilage Degeneration Score (OARSI CDS). Additionally, as CRS maps the full surface, it was used to simulate the level of uncertainty in histological sampling. ResultsCRS and OARSI CDS have a linear relationship. CRS for healthy cartilage is 2.75 (95% CI: 1.14-4.36) and with every 1 unit increase in OARSI, CRS is expected to increase by 0.64 (95% CI: 0.35-0.92). Cartilage degeneration due to CIOA was evident in both histopathological scoring and CRS. However, only CRS was sensitive enough to show consistent damage progression from day 10 to day 60. Furthermore, our simulation for histological sampling suggested that up to 16 coronal slices with 200µm spacing would be needed to accurately represent the full extent of cartilage surface degeneration in a slice wise manner. Gait analysis showed changes solely at eight days post-collagenase injection, normalizing by day 60. ConclusionThe CRS analysis method emerges as a robust tool for cartilage surface damage assessment. This study demonstrates the potential of automatic 3D analysis over the traditional 2D histological approach when evaluating cartilage surface damage. Data statementMicro-computed tomography data is available via ida.fairdata.fi46 (https://doi.org/10.23729/f33d3ba8-01b8-47af-90dd-94b7c7861247)

Association of Cartilage, Synovial Fluid and Membrane Pathological Findings in Serbian Mountain Horses Without Signs of Lameness

Abstract Osteoarthritis (OA) in horses often affects the metacarpal/metatarsophalangeal (MCP/MTP) joints and its detection in the early stages is crucial for effective management. I t was hypothesized that the extent of cartilage damage positively correlates with synovial membrane (SM) and synovial fluid (SF) pathological findings in the MCP/MTP joints of Serbian mountain horses that transported heavy loads but did not show signs of lameness. The study was conducted on 32 MCP/MTP joints of eight horses between seven to 12 years of age. Horse limbs were transferred from the abattoir to the necropsy room and SF was sampled. Its appearance, total nucleated cell count (TNCC), mononuclear cell count (MNC), total proteins (TP), and haptoglobin (Hp) were determined. Samples of SM were collected from the dorsal palmar/plantar pouch for histology. A macroscopic examination of gross condylar pathology of the third metacarpal/metatarsal bone was performed with Indian Ink staining. Scoring was done based on Osteoarthritis Research Society International recommendations. SF was clear, pale yellow, and mostly fairly viscous. Half of the samples had TNCC above, and all had TP within the reference range. Hp values were below the reference range and were omitted from further analyses. TNCC correlated with MNC (ρs=0.81, P&lt;0.001), microscopic (ρs=0.62, P=0.003) and macroscopic scores (ρs=0.47, P=0.008). In addition, MNC correlated with macroscopic scores (ρs=0.40, P=0.03). All pathological findings were mild and their correlation indicated that these processes are interrelated and that could be ascribed to early OA.

The Genetics and Functional Genomics of Osteoarthritis.

Osteoarthritis is the most prevalent whole-joint degenerative disorder, and is characterized by the degradation of articular cartilage and the underlying bone structures. Almost 600 million people are affected by osteoarthritis worldwide. No curative treatments are available, and management strategies focus mostly on pain relief. Here, we provide a comprehensive overview of the available human genetic and functional genomics studies for osteoarthritis to date and delineate how these studies have helped shed light on disease etiopathology. We highlight genetic discoveries from genome-wide association studies and provide a detailed overview of molecular-level investigations in osteoarthritis tissues, including methylation-, transcriptomics-, and proteomics-level analyses. We review how functional genomics data from different molecular levels have helped to prioritize effector genes that can be used as drug targets or drug-repurposing opportunities. Finally, we discuss future directions with the potential to drive a step change in osteoarthritis research.

NUMB attenuates posttraumatic osteoarthritis by inhibiting BTRC and inactivating the NF-κB pathway

Posttraumatic osteoarthritis (PTOA) is closely related to the inflammatory response caused by mechanical injury and leads to joint degeneration. Herein, we aimed to evaluate the role and underlying mechanism of NUMB in PTOA progression. Anterior cruciate ligament transection (ACLT)-induced rats and interleukin (IL)-1β-treated chondrocytes were used as in vivo and in vitro models of PTOA, respectively. The NUMB overexpression plasmid (pcDNA-NUMB) was administered by intra-articular injection to PTOA model rats, and safranin O-fast green staining, the Osteoarthritis Research Society International (OARSI) scoring system, and HE staining were used to evaluate the severity of cartilage damage. The secretion of inflammatory cytokines (TNF-α, IL-1β, and IL-6) and chondrocyte-specific markers (MMP13 and COL2A1) was detected via ELISA. Cell viability and apoptosis were evaluated by MTT and TUNEL assays. NUMB was expressed at lower levels in ACLT-induced PTOA rats and in IL-1β-treated chondrocytes than in control rats and cells. NUMB overexpression enhanced cell viability and reduced cell apoptosis, inflammation and cartilage degradation in chondrocytes stimulated by IL-1β. NUMB bound to BTRC to promote p-IκBα expression, resulting in NF-κB pathway inactivation. BTRC overexpression reversed the promoting effect of NUMB overexpression on cell viability and the inhibitory effects of NUMB overexpression on apoptosis, inflammation and cartilage degradation in IL-1β-induced chondrocytes. In addition, overexpression of NUMB alleviated articular cartilage damage by repressing inflammation and cartilage degradation in ACLT-induced PTOA rats. Our data indicated that NUMB regulated PTOA progression through the BTRC/NF-κB pathway, which may be a viable therapeutic target in PTOA.

Does Proprioception-Based Rehabilitation Enhance Functional Outcome in Total Knee Arthroplasty? A Prospective Randomised Study.

Rehabilitation after Total Knee Arthroplasty (TKA) often includes proprioceptive exercises to prevent falls, but studies on proprioceptive training have yielded conflicting findings. This study aims to explore impact of proprioceptive training on functional performance after TKA. Eighty patients who underwent unilateral TKA were randomly assigned to a proprioceptive exercise (PE) group or a routine exercises (RE) group. The PE group received proprioceptive exercises in addition to routine physiotherapy. Osteoarthritis Research Society Internal (OARSI) recommended tests and Oxford Knee Score (OKS) were used to assess performance and outcome at 3 and 6months. In the 30-s chair sits test, the PE group outperformed the RE group at 3months (13.69 vs. 9.17) and 6months (21.07 vs. 18.63) (p < 0.001 and p = 0.030). Stair climbing favoured PE group at 3months (8.86 vs. 16.66, p = 0.037) and 6months (0.556 vs. 1.133, p = 0.001). At 6months in the 40-m fast-paced walk test, the PE group had a significantly shorter time (0.308min vs. 0.557min, p < 0.001). Timed up and go test at 6months favoured PE group (0.204min vs. 0.377min). In the 6-min walk test, the PE group covered significantly greater distances than the RE group at 3months (589.59 vs. 346.53m, p < 0.001) and 6months (649.60 vs. 448.32m, p < 0.001). OKS at 3months was 38 ± 2.0 for PE group and 38 ± 4 for RE group (p = 1). OKS at 6months was 42 ± 4 for PE group and 40 ± 2 for RE group (p = 0.94). This study highlights the importance of proprioception-based rehabilitation in improving functional performance for TKA patients, surpassing traditional rehabilitation programmes.