Osteoarthritis Process Research Articles

Enhanced joint pain in diabetic patients with knee osteoarthritis is associated with increased synovitis, synovial immune cell infiltration, and erythrocyte extravasation.

Diabetes mellitus (DM) is an important risk factor for the development of osteoarthritis (OA), increasing OA progression and OA pain. To gain insight into the underlying mechanisms of how DM exacerbates OA processes and OA pain, this study analyzed histological differences of synovial tissues from non-DM and DM patients with OA and correlated these differences with knee pain severity. Synovial tissue was obtained from 12 non-DM and 10 DM patients with advanced knee OA who underwent total knee arthroplasty. Synovial inflammation was assessed using the Synovitis score developed by Krenn. The Knee Injury and Osteoarthritis Outcome Score (KOOS) was used to assess knee pain intensity and disability in OA patients. The number of mast cells, macrophages, nerve fibers, capillaries, larger vessels and erythrocyte extravasation were analyzed microscopically in histological and immunostained synovial sections from non-DM and DM patients. Association analyses were performed to determine associations between OA knee pain and synovial changes affected by DM. Synovial tissue from OA patients with DM had a higher synovitis score, more erythrocyte extravasation, and contained higher numbers of mast cells and macrophages compared to non-DM patients. The number of capillaries and vessels in the lining/sublining layer of the synovial tissue was reduced in DM patients. OA patients with DM had more severe knee pain compared to non-DM patients. The KOOS pain score was associated with the synovitis score, the number of tissue macrophages, and the number of mast cells in the synovial tissue (adjusted for age, sex, and BMI). In addition, the erythrocyte extravasation score was associated with the KOOS pain score and with the synovitis score. The study suggests that increased OA progression and pain severity in patients with DM result from more pronounced synovitis and synovial vascular leakage and increased infiltration of macrophages and mast cells.

M7G-modified mt-tRF3b-LeuTAA regulates mitophagy and metabolic reprogramming via SUMOylation of SIRT3 in chondrocytes

N7-methylguanosine (m7G) modification is one of the most prevalent RNA modifications, and methyltransferase-like protein-1 (METTL1) is a key component of the m7G methyltransferase complex. METTL1-catalyzed m7G as a new RNA modification pathway that regulates RNA structure, biogenesis, and cell migration. Increasing evidence indicates that m7G modification has been implicated in the pathophysiological process of osteoarthritis (OA). However, the underlying molecular mechanisms of m7G modification remains incompletely elucidated during the progression of OA. Here we found that METTL1 and m7G levels were markedly increased in OA chondrocytes. In addition, METTL1-mediated m7G modification upregulated mt-tRF3b-LeuTAA expression to exacerbate chondrocyte degeneration. Mechanistically, mt-tRF3b-LeuTAA decreased the SUMO-specific protease 1 (SENP1) protein expression and upregulated the level of sirtuin 3 (SIRT3) SUMOylation to inhibit PTEN induced kinase 1 (PINK1)/Parkin-mediated mitochondrial mitophagy. Intra-articular injection of PMC-tRF3b-LeuTAA inhibitor (Polyamidoamine-polyethylene glycol surface-modified with Minimal self-peptides and Chondrocyte-affinity peptides, PMC) attenuated destabilization of the medial meniscus (DMM) mouse cartilage degeneration in vivo. Our study demonstrates that METTL1/m7G/mt-tRF3b-LeuTAA axis accelerate cartilage degradation by inhibiting mitophagy and promoting mitochondrial dysfunction through SIRT3 SUMOylation, and suggest that targeting METTL1 and its downstream signaling axis could be a promising therapeutic target for OA treatment.

Role and mechanism of Actein on condylar bone metabolism in APOE deletion-induced osteoporotic mice

AimsTo investigate the effects of Actein from Cimicifugae Rhizoma on condylar bone and cartilage in APOE deletion-induced osteoporotic mice, and to preliminarily explore the underlying mechanism. MethodsSixty 8-week-old female mice were used, which underwent APOE−/− and ovariectomy procedures, followed by oral administration of Actein (15 mg/kg) and Atorvastatin Calcium (AC, 3 mg/kg) for eight weeks. Body weight, uterine weight, and systemic indexes related to bone metabolism and lipid metabolism were assessed in each group. Changes in condylar bone histomorphometric parameters were evaluated using Micro-CT. Morphological changes in the condyle were observed with Hematoxylin-Eosin (H&E), Safranin O/Fast Green, and Alcian Blue Hematoxylin/Orange G (ABH/OG) staining, with OARSI pathology scoring performed. Sirius red staining and immunofluorescence were used to determine the expression levels of Collagen I (Col I) and Collagen III (Col III) in bone matrix, and Col II in cartilage matrix. Immunohistochemistry assessed the relative expression levels of ALP and proteins associated with the Wnt/β-catenin/RUNX2 signaling pathway. ResultsAPOE−/− exacerbates ovariectomy -induced osteoporosis (OP) in condylar of mice. Actein and AC significantly reversed OP, improved bone mineral density (BMD), increased bone microarchitecture, and restored abnormal calcium and phosphorus metabolism in the blood and urine. Morphologically, APOE−/− and ovariectomy reduced condylar cartilage thickness, disrupted chondrocyte arrangement, chondrocyte cleavage, and clustered aggregation, resembling osteoarthritis (OA)-like changes. Actein and AC partially restored the disrupted chondrocyte arrangement, smoothed chondrocyte cleavage, and up-regulated the levels of chondrocyte matrix (Col II, aggrecan) and bone matrix (Col III, ALP). Actein reversed the OA process, potentially through the Wnt/β-catenin/RUNX2 signaling pathway. ConclusionAPOE−/− and ovariectomy induced OP, leading to OA-like lesions in condylar of mice. Actein promoted cartilage repair and trabecular bone recovery by increasing extracellular matrix synthesis (Col II, Col III, aggrecan), reversing the OA process, possibly through the Wnt/β-catenin/RUNX2 signaling pathway.

Thioredoxin-Interacting Protein's Role in NLRP3 Activation and Osteoarthritis Pathogenesis by Pyroptosis Pathway: In Vivo Study.

Thioredoxin-interacting protein (TXNIP) has been involved in oxidative stress and activation of the NOD-like receptor protein-3 (NLRP3) inflammasome, directly linking it to the pyroptosis pathway. Furthermore, pyroptosis may contribute to the inflammatory process in osteoarthritis (OA). The purpose of this study was to investigate the role of TXNIP in activating the NLRP3 inflammasome through the pyroptosis pathway in an OA rat model. Destabilization of the medial meniscus (DMM) was induced in the OA model with intra-articular injections of adeno-associated virus (AAV) overexpressing (OE) or knocking down (KD) TXNIP. A total of 48 healthy rats were randomly divided into six groups (N = 8 each). During the experiment, the rats' weights, mechanical pain thresholds, and thermal pain thresholds were measured weekly. Morphology staining, micro-CT, 3D imaging, and immunofluorescence (IF) staining were used to measure the expression level of TXNIP, and ELISA techniques were employed. OE-TXNIP-AAV in DMM rats aggravated cartilage destruction and subchondral bone loss, whereas KD-TXNIP slowed the progression of OA. The histological results showed that DMM modeling and OE-TXNIP-AAV intra-articular injection caused joint structure destruction, decreased anabolic protein expression, and increased catabolic protein expression and pyroptosis markers. Conversely, KD-TXNIP-AAV slowed joint degeneration. OE-TXNIP-AVV worsened OA by accelerating joint degeneration and damage, while KD-TXNIP-AAV treatment had a protective effect.

Biomarkers for hypertrophic chondrocyte differentiation are associated with spatial cellular organisation and suggest endochondral ossification-like processes in osteoarthritic cartilage: An exploratory study

BackgroundIn healthy articular cartilage, chondrocytes are found along arcades of collagen fibers as Single Strings. With onset of cartilage degeneration this pattern changes to Double Strings. In the course of osteoarthritis Small Clusters, and finally Big Clusters form. In highly degenerated articular cartilage, another poorly understood pattern is found where chondrocyte morphology differs considerably, and the distribution of cells is diffuse. Progression of osteoarthritis is accompanied by key processes such as chondrocyte proliferation, apoptosis, hypertrophic differentiation, inflammation, and angiogenesis. The aim of this exploratory study was to identify biomarkers for these processes in the context of spatial cellular organizational changes in articular cartilage. MethodsCartilage explants (n = 166 patients) were sorted according to their predominant cellular pattern. Quantitative or semi-quantitative analysis of 39 biomarkers were performed by multiplex assay (31) or ELISA (8), and qualitative analysis on 12 immunohistochemical markers. ResultsHypertrophic differentiation (e.g. type-X collagen, osteopontin, osteocalcin and interleukin-6) and angiogenesis were associated with changes in chondrocyte organisation. First changes take place already at the transition from Single Strings to Double Strings. Drastic changes in the appearance of numerous biomarkers are found at the transition from Big Clusters to Diffuse. ConclusionKey processes in osteoarthritis and their biomarkers seem to depend on the spatial distribution of chondrocytes in articular cartilage. Abrupt changes in biomarker occurrence were observed between Big Clusters and Diffuse insinuating that the Diffuse pattern is composed of a different cell population or at least a different form of chondrocyte morphology. The Translational Potential of this ArticleIn situ identification of the different spatial chondrocyte patterns by fluorescence microscopy has already been established in the recent past. Analysing human in-situ cartilage explants rather than isolated OA chondrocytes closes the gap between in vitro and in vivo studies and as such, stretches a big step towards translation of the observed findings. The direct association between tissue biomarker profile and cellular arrangements representing different states of OA sheds new light on the molecular and cellular physiopathology, especially in the context of larger processes such as angiogenesis, cellular proliferation, differentiation, and apoptosis. This also opens an interesting perspective for future investigation of such biomarkers and processes in clinical studies.

Knee Osteoarthritis.

Knee osteoarthritis (OA) typically presents with joint pain that is exacerbated by use and alleviated with rest. There is relatively brief, self-limited morning stiffness and absence of constitutional symptoms. Overweight and obesity are the most important modifiable risk factors. Although pharmacologic and nonpharmacologic interventions are generally effective at alleviating pain and improving physical function, they do not fundamentally reverse the pathologic and radiographic process of knee OA. As the severity of disease increases, the magnitude of pain and functional impairment intensifies. Surgical intervention should be pursued to relieve pain and restore functionality only when nonpharmacologic approaches and pharmacologic agents fail to control pain.

Melatonin Alleviates Osteoarthritis by Regulating NADPH Oxidase 4-Induced Ferroptosis and Mitigating Mitochondrial Dysfunction.

Recent evidence indicates that the damaged regions in osteoarthritis are accompanied by the accumulation of iron ions. Ferroptosis, as an iron-dependent form of cell death, holds significant implications in osteoarthritis. Melatonin, a natural product with strong scavenging abilities against reactive oxygen species and lipid peroxidation, plays a crucial role in the treatment of osteoarthritis. This study aims to demonstrate the existence of ferroptosis in osteoarthritis and explore the specific mechanism of melatonin in suppressing ferroptosis and alleviating osteoarthritis. Our findings reveal that melatonin reverses inflammation-induced oxidative stress and lipid peroxidationwhile promoting the expression of extracellular matrix components in chondrocytes, safeguarding the cells. Our research has revealed that NADPH oxidase 4 (NOX4) serves as a crucial molecule in the ferroptosis process of osteoarthritis. Specifically, NOX4 is located on mitochondria in chondrocytes, which can induce disorders in mitochondrial energy metabolism and dysfunction, thereby intensifying oxidative stress and lipid peroxidation. LC-MS analysis further uncovered that GRP78 is a downstream binding protein of NOX4. NOX4 induces ferroptosis by weakening GRP78's protective effect on GPX4 and reducing its expression. Melatonin can inhibit the upregulation of NOX4 on mitochondria and mitigate mitochondrial dysfunction, effectively suppressing ferroptosis and alleviating osteoarthritis. This suggests that melatonin therapy represents a promising new approach for the treatment of osteoarthritis.

Bergenin protects against osteoarthritis by inhibiting STAT3, NF-κB and Jun pathways and suppressing osteoclastogenesis

Osteoarthritis (OA) is a chronic degenerative disease characterized by articular cartilage destruction and subchondral bone reconstruction in the early stages. Bergenin (Ber) is a cytoprotective polyphenol found in many medicinal plants. It has been proven to have anti-inflammatory, antioxidant, and other biological activities, which may reveal its potential role in the treatment of OA. This study aimed to determine the potential efficacy of Ber in treating OA and explore the possible underlying mechanism through network pharmacology and validation experiments. The potential co-targets and processes of Ber and OA were predicted by using network pharmacology, including a Venn diagram for intersection targets, a protein‒protein interaction (PPI) network to obtain key potential targets, and GO and KEGG pathway enrichment to reveal the probable mechanism of action of Ber on OA. Subsequently, validation experiments were carried out to investigate the effects and mechanisms of Ber in treating OA in vitro and vivo. Ber suppressed IL-1β-induced chondrocyte apoptosis and extracellular matrix catabolism by inhibiting the STAT3, NF-κB and Jun signalling pathway in vitro. Furthermore, Ber suppressed the expression of osteoclast marker genes and RANKL-induced osteoclastogenesis. Ber alleviated the progression of OA in DMM-induced OA mice model. These results demonstrated the protective efficacy and potential mechanisms of Ber against OA, which suggested that Ber could be adopted as a potential therapeutic agent for treating OA.

New insights into the mechanisms and therapeutic strategies of chondrocyte autophagy in osteoarthritis.

Osteoarthritis (OA) is a chronic joint disease with an unclear cause characterized by secondary osteophytes and degenerative changes in the articular cartilage. More than 250 million people are expected to be affected by it by 2050, putting a tremendous socioeconomic strain on the entire world. OA cannot currently be treated with any effective medications that change the illness. Over time, chondrocytes undergo gradual metabolic, structural, and functional changes as a result of aging or abuse. The degenerative progression of osteoarthritis is significantly influenced by the imbalance of chondrocyte homeostasis. By continuously recycling and rebuilding macromolecules or organelles, autophagy functions as a crucial regulatory system to maintain homeostasis during an individual's growth and development. This review uses chondrocytes as its starting point and establishes a strong connection between autophagy and osteoarthritis in order to thoroughly examine the mechanisms behind chondrocyte autophagy in osteoarthritis. Biomarkers of chondrocyte autophagy will be identified, and prospective targeted medications and novel treatment approaches for slowing or preventing the course of OA will be developed based on chondrocyte senescence, autophagy, and apoptosis in OA. KEY MESSAGES: Currently, OA has not been treated with any drugs that can effectively cure it. We hope that by exploring specific targets in the course of osteoarthritis, we can promote the progress of treatment strategies. The degenerative progression of osteoarthritis is significantly influenced by the imbalance of chondrocyte balance. Through the continuous recovery and reconstruction of macromolecules or organelles, autophagy is an important regulatory system for maintaining homeostasis during individual growth and development. In this paper, the close relationship between autophagy and osteoarthritis was established with chondrocytes as the starting point, in order to further explore the mechanism of chondrocyte autophagy in osteoarthritis. The development process of osteoarthritis was studied from the perspective of chondrocytes, and the change of autophagy level had a significant impact on osteoarthritis. Chondrocyte autophagy is mainly determined by intracellular mitochondrial autophagy, so we are committed to finding relevant molecules. Through PI3K/AKT- and MAPK-related pathways, the biomarkers of chondrocyte autophagy were identified, and chondrocyte senescence, autophagy, and apoptosis based on osteoarthritis provided a constructive idea for the development of prospective targeted drugs and new therapies to slow down or prevent the progression of osteoarthritis.

Development of an Ultrasound Imaging Atlas for Grading Osteoarthritis in the First Metatarsophalangeal Joint.

Ultrasound (US) imaging may play a fundamental role in the earlier detection and assessment of first metatarsophalangeal joint (MTPJ) osteoarthritis (OA) because of its ability to depict tissue-specific morphologic changes before the point of irreversible structural damage. However, the role of US in supporting the diagnosis of OA in foot joints has not been clearly defined. The aims of this study were to develop a semiquantitative US atlas (the AUT ultrasound imaging [AUTUSI] atlas) to grade the degree of osteoarthritic change in the first MTPJ and to evaluate the intraexaminer and interexaminer reproducibility of using the atlas. US images were obtained from 57 participants (30 participants with radiographically confirmed first MTPJ OA). The AUTUSI atlas supports the examination of grading joint effusion, synovial hypertrophy, synovitis, osteophytes, joint space narrowing, and cartilage thickness. Six examiners used the atlas to independently grade 24 US images across 2 sessions. Intraexaminer and interexaminer reproducibility were determined using percentage agreement and Gwet's AC2. Observations using the AUTUSI atlas demonstrated almost perfect-to-perfect interexaminer agreement (percentage agreement ranged from 96% to 100%, and Gwet's AC2 values ranged from 0.81 to 1.00) and moderate-to-perfect intraexaminer agreement (percentage agreement ranged from 67% to 100%, and Gwet's AC2 values ranged from 0.54 to 1.00). The AUTUSI atlas demonstrated excellent intraexaminer and interexaminer reproducibility for evaluating first MTPJ joint effusion, synovial hypertrophy, synovitis, joint space narrowing, osteophytes, and cartilage thickness. The AUTUSI atlas affords an opportunity to detect prognostic markers of OA earlier in the disease cascade and has the potential to advance understanding of the pathologic process of first MTPJ OA.

Estrogen receptor is involved in the osteoarthritis mediated by Atg16L1-NLRP3 activation.

This study aims to explore the mechanisms of dual regulation of osteoarthritis (OA) progression by the involvement of estrogen receptor (ER) in autophagy and inflammation. Bioinformatics methods were used to explore the relationship among associated genes. Western blot assays were used to detect related protein expression of OA in C28I2 and induced OA cellular model. Real-time quantitative polymerase chain reaction (RT-qPCR) analysis were used to detect OA related gene expression in C28I2 and induced OA cellular model. Co-immunoprecipitation (CO-IP) analysis were used to verify the direct interaction between ER and NOD-like receptor thermal protein domain associated protein 3 (NLRP3). The C28I2 cellular model of OA was induced by interleukin-1β (IL-1β). The small interfering ribonucleic acid (SiRNA)-mediated knockdown of autophagy-related 16 like 1 (ATG16L1) in C28I2 decreased the expression of MAP1LC3B (LC3B) and NLRP3. Besides, ER-beta (ERβ) agonist changed the gene expression of NLRP3 and ATG16L1. Moreover, CO-IP analysis indicated the direct interaction between ER and NLRP3. Our study results revealed that ATG16L1, NLRP3, and IL-1β interacted closely and ERβ was involved in OA process by affecting autophagy and inflammatory activation.

Genicular Artery Embolization: A New Tool for the Management of Refractory Osteoarthritis-Related Knee Pain.

Osteoarthritis (OA) of the knee is a prevalent cause of chronic pain and disability, particularly affecting women. While traditionally attributed to chronic wear and tear, recent evidence highlights multifactorial pathogenesis involving low-grade inflammation and neoangiogenesis. Current therapeutic options include physical therapy, pharmacotherapy, and total knee arthroplasty (TKA). However, a subset of patients remain symptomatic despite conservative measures, necessitating the development of minimally invasive interventions. Genicular artery embolization (GAE) emerges as a promising option, targeting neovascularization and inflammatory processes in OA. This paper reviews the pathophysiological basis, patient selection criteria, procedural details, and outcomes of GAE. Notably, GAE demonstrates efficacy in relieving knee pain and improving function in patients refractory to conventional therapy. While further research is warranted to elucidate its long-term outcomes and compare it with existing modalities, GAE represents a novel approach in the management of symptomatic knee OA, potentially delaying or obviating the need for surgical intervention. Here, we synthesize the relevant literature, technical details of the procedure, and future perspectives. Moreover, the success of GAE prompts the exploration of transarterial embolization in other musculoskeletal conditions, underscoring the evolving role of interventional radiology in personalized pain management strategies.

A call for standardization for secretome and extracellular vesicles in osteoarthritis: results show disease-modifying potential, but protocols are too heterogeneous-a systematic review.

The currently available osteoarthritis (OA) treatments offer symptoms' relief without disease-modifying effects. Increasing evidence supports the role of human mesenchymal stem cells (MSCs) to drive beneficial effects provided by their secretome and extracellular vesicles (EVs), which includes trophic and biologically active factors. Aim of this study was to evaluate the in vitro literature to understand the potential of human secretome and EVs for OA treatment and identify trends, gaps, and potential translational challenges. A systematic review was performed on PubMed, Embase, and Web-of-Science, identifying 58 studies. The effects of secretome and EVs were analysed on osteoarthritic cells regarding anabolic, anti-apoptotic/anti-inflammatory and catabolic/pro-inflammatory/degenerative activity, chondroinduction, and immunomodulation. The results showed that MSC-derived EVs elicit an increase in proliferation and migration, reduction of cell death and inflammation, downregulation of catabolic pathways, regulation of immunomodulation, and promotion of anabolic processes in arthritic cells. However, a high heterogeneity in several technical or more applicative aspects emerged. In conclusion, the use of human secretome and EVs as strategy to address OA processes has overall positive effects and disease-modifying potential. However, it is crucial to reduce protocol variability and strive toward a higher standardization, which will be essential for the translation of this promising OA treatment from the in vitro research setting to the clinical practice.

Bioinformatic analysis combined with immune infiltration to explore osteoarthritis biomarkers and drug prediction.

Along with global aging, osteoarthritis (OA) appears to have a high incidence and disability rate, which seriously affects the quality of life of patients, making age a major risk factor. However, the pathology of OA is under-researched, and there is no obvious and effective treatment. Research has demonstrated the importance of aging, inflammation, and immunology in the onset and course of OA. This study aims to anticipate therapeutic drugs based on critical genes associated with OA and to elucidate the roles of genes and possible biomarkers associated with inflammation, immunology, and cellular senescence in OA. The OA gene expression matrix was first obtained from the Gene Expression Omnibus database. Screening for OA significant differentially expressed genes by bioinformatics identification. Specific biological processes and related signaling pathways of the differential genes were enriched. Then elucidate the status of immune cell involvement in OA based on immune infiltration analysis. Finally predict therapeutic agents based on pivotal genes. A total of 198 differentially expressed genes were identified in OA, and TP53, EGFR, TGFB1, LEP, CD4, MAPK8, SCARB1, ADIPOQ, JAK2, and SERPINE1 were further identified as important hub genes. The enrichment results showed that the development of arthritis was mainly related to immune cell differentiation, amino acid metabolism and cellular senescence process. The validation of immune infiltration results indicated that NK_cells, CD4_Tcells, Macrophages, Monocytic_lineage, Dendritic_cells, Basophils, CD8+_naive_T-cells may play an important role in the immune process of OA. Key Drug Prediction of Hub Genes found that Halicin, Ruxolitinib, Tofacitinib, Clenoliximab, Baricitinib may be a key drug or component in the treatment of OA.

The emerging role of the semaphorin family in cartilage and osteoarthritis.

In the pathogenesis of osteoarthritis, various signaling pathways may influence the bone joint through a common terminal pathway, thereby contributing to the pathological remodeling of the joint. Semaphorins (SEMAs) are cell-surface proteins actively involved in and primarily responsible for regulating chondrocyte function in the pathophysiological process of osteoarthritis (OA). The significance of the SEMA family in OA is increasingly acknowledged as pivotal. This review aims to summarize the mechanisms through which different members of the SEMA family impact various structures within joints. The findings indicate that SEMA3A and SEMA4D are particularly relevant to OA, as they participate in cartilage injury, subchondral bone remodeling, or synovitis. Additionally, other elements such as SEMA4A and SEMA5A may also contribute to the onset and progression of OA by affecting different components of the bone and joint. The mentioned mechanisms demonstrate the indispensable role of SEMA family members in OA, although the detailed mechanisms still require further exploration.

Omega-3 Supplementation and Its Effects on Osteoarthritis.

Osteoarthritis (OA) is a degenerative joint disease characterized by the destruction of the articular cartilage, resulting in a pro-inflammatory response. The progression of OA is multifactorial and is influenced by the underlying cause of inflammation, which includes but is not limited to trauma, metabolism, biology, comorbidities, and biomechanics. Although articular cartilage is the main tissue affected in osteoarthritis, the chronic inflammatory environment negatively influences the surrounding synovium, ligaments, and subchondral bone, further limiting their functional abilities and enhancing symptoms of OA. Treatment for osteoarthritis remains inconsistent due to the inability to determine the underlying mechanism of disease onset, severity of symptoms, and complicating comorbidities. In recent years, diet and nutritional supplements have gained interest regarding slowing the disease process, prevention, and treatment of OA. This is due to their anti-inflammatory properties, which result in a positive influence on pain, joint mobility, and cartilage formation. More specifically, omega-3 polyunsaturated fatty acids (PUFA) have demonstrated an influential role in the progression of OA, resulting in the reduction of cartilage destruction, inhibition of pro-inflammatory cytokine cascades, and production of oxylipins that promote anti-inflammatory pathways. The present review is focused on the assessment of evidence explaining the inflammatory processes of osteoarthritis and the influence of omega-3 supplementation to modulate the progression of osteoarthritis.

MedKnee: A New Deep Learning-Based Software for Automated Prediction of Radiographic Knee Osteoarthritis.

In computer-aided medical diagnosis, deep learning techniques have shown that it is possible to offer performance similar to that of experienced medical specialists in the diagnosis of knee osteoarthritis. In this study, a new deep learning (DL) software, called "MedKnee" is developed to assist physicians in the diagnosis process of knee osteoarthritis according to the Kellgren and Lawrence (KL) score. To accomplish this task, 5000 knee X-ray images obtained from the Osteoarthritis Initiative public dataset (OAI) were divided into train, valid, and test datasets in a ratio of 7:1:2 with a balanced distribution across each KL grade. The pre-trained Xception model is used for transfer learning and then deployed in a Graphical User Interface (GUI) developed with Tkinter and Python. The suggested software was validated on an external public database, Medical Expert, and compared with a rheumatologist's diagnosis on a local database, with the involvement of a radiologist for arbitration. The MedKnee achieved an accuracy of 95.36% when tested on Medical Expert-I and 94.94% on Medical Expert-II. In the local dataset, the developed tool and the rheumatologist agreed on 23 images out of 30 images (74%). The MedKnee's satisfactory performance makes it an effective assistant for doctors in the assessment of knee osteoarthritis.

Extracorporeal Shock Wave Therapy as Regenerative Medicine in Knee Osteoarthritis: Pre-Experiment for Matrix Metalloproteinase-3 Evaluation.

Knee osteoarthritis (KOA) is currently treated by regenerative therapies that aim to inhibit arthritic degeneration. Extracorporeal shock wave therapy (ESWT) is one of the physical regenerative approaches used for KOA management. However, little is known regarding the impact of shock wave treatment on matrix metalloproteinase-3 (MMP-3), which is one of the enzymes mediating cartilage degradation. To evaluate the effect of ESWT on MMP-3 levels and pain intensity in patients with KOA. Fourteen patients diagnosed with Kellgren Lawrence, grades 2 and 3 KOA were recruited for the study. ESWT piezo shockwave was applied once a week for six weeks. MMP-3 levels in the blood were measured pre-test, mid-test (three weeks after therapy) and post-test (one week after the last session) by enzyme-linked immunosorbent assay (ELISA). The perceived pain was recorded at each session by the Wong Becker Face Scale. The median pre-test, mid-test and post-test MMP-3 levels were 19.92 ng/mL, 15.89 ng/mL and 18.82 ng/mL, respectively, and there were significant differences between the pre-test and mid-test, and the pre-test and post-test values (p < 0.05). The pain scores also decreased significantly over the period of intervention. MMP-3 levels decreased significantly in KOA patients after ESWT, and the decline was most obvious after 3 weeks of therapy. Therefore, EWST should be considered as a suitable treatment option for KOA.

Identification of biomarkers and immune infiltration characterization of lipid metabolism-associated genes in osteoarthritis based on machine learning algorithms.

Osteoarthritis (OA) is a prevalent degenerative condition commonly observed in the elderly, leading to consequential disability. Despite notable advancements made in clinical strategies for OA, its pathogenesis remains uncertain. The intricate association between OA and metabolic processes has yet to receive comprehensive exploration. In our investigation, we leveraged public databases and applied machine learning algorithms, including WGCNA, LASSO, RF, immune infiltration analysis, and pathway enrichment analysis, to scrutinize the role of lipid metabolism-associated genes (LAGs) in the OA. Our findings identified three distinct biomarkers, and evaluated their expression to assess their diagnostic value in the OA patients. The exploration of immune infiltration in these patients revealed an intricate relationship between immune cells and the identified biomarkers. In addition, in vitro experiments, including qRT-PCR, Western blot, chondrocyte lipid droplets detection and mitochondrial fatty acid oxidation measurement, further verified abnormal expressions of selected LAGs in OA cartilage and confirmed the correlation between lipid metabolism and OA.

SUCCINATE-RECEPTOR SYSTEM OF BONE AND CARTILAGE TISSUE IN PATIENTS WITH METABOLIC PHENOTYPE OF OSTEOARTHRITIS

Introduction. Currently, osteoarthritis (OA) has been identified as a polyetiological disease, where several phenotypes have been identified based on the leading frequency. Obviously, each clinical phenotype corresponds only to its fundamental changes on the part of various organs and systems. Un-til recently, special attention was paid to the study of metabolic processes in osteoarthritis (OA) and was paid to the state of the cartilage, but more and more interest was focused on the biochemistry of the subchondral bone, its microarchitectonics and signal function. Aid. To study the features of the manifestation of the succinate-receptor system of bone and cartilage tissue in patients with the metabolic phenotype of osteoarthritis. Material and methods. 42 patients took part in the study and were divided into 2 groups: 1 group – patients without articular disease, normal body mass index; 2 group – patients with metabolic phenotype of OA. The subjects were collected complaints, anamnesis, as well as general clinical and orthopedic examination. The levels of succinate, succinate receptor (SUCNR1) and succinate dehydrogenase (SDH) are measured in bone and cartilage tissue homogenates. Results. In the 2 group, an increase in SUCNR1 expression was detected in all studied areas of the joint in comparison with the 1 group. In the 2 group, the differences were tissue-specific in the distribution of SUCNR1 with a predominant increase in the amount of the receptor in the subchondral bone compared to the loaded (p=0.031) and non-loaded zone of cartilage (p=0.001). In the 1 group, the studied areas of cartilage and bone did not dif-fer in the amount of SUCNR1 from each other. In the group of patients with the metabolic phenotype of OA, an increase in mitochondrial succinate was found both in the subchondral bone tissue and in different zones of cartilage compared to the 1 group. The final indicators of SDH activity in the mito-chondria of the studied joint zones that we obtained turned out to be low in both groups, however, relatively high enzyme activity was observed in the subchondral zone of the bone of the group of metabolic phenotype of OA. Conclusion. In patients with the metabolic phenotype of OA, high expression of SUCNR1 in joint tissues is observed, which is tissue-specific with a predominant increase in the amount of SUCNR1 in the subchondral bone. We found higher levels of succinate in the subchondral bone and cartilaginous areas of joints in patients with the metabolic phenotype of OA and suggest that the succinate-SUCNR1 interaction in affected joints in OA is adaptive in nature.