Acetabular Bone Cement Extension Leading to Bladder Obstruction: An Orthopedic Surgical Complication.

Polymethyl methacrylate, commonly known as bone cement, is widely used for implant fixation in orthopedic and trauma surgery due to its excellent adhesive properties and biocompatibility. However, complications such as bone cement extrusion, although rare, can lead to significant morbidity. We present the case of an 86-year-old Hispanic female who presented to the emergency department (ED) with tachycardia, hypertension, and respiratory distress. Her medical history included Parkinson's disease, hiatal hernia, osteoarthritis, colon cancer, and a complex post-hip fracture surgical history. Despite being bedridden, she had been previously in stable health. A computed tomography (CT) scan revealed a significant hiatal hernia, minimal remaining left lung tissue, a right lung nodule, hydronephrosis, and a large radiopaque mass in the right pelvis extending from the acetabular area. This radiopaque mass was later determined to be bone cement, with a portion extruding into the bladder. The patient was diagnosed with sepsis secondary to a urinary tract infection and hyponatremia; a urology consultation recommended a conservative approach to avoid potential antibiotic resistance. This case report highlights a rare complication of total hip arthroplasty involving bone cement extrusion into the bladder, which led to hydronephrosis and a urinary tract infection (UTI). Although such complications can be asymptomatic, they should be considered in patients with a history of arthroplasty.

PU.1 regulates osteoarthritis progression via CSF1R in synovial cells.

This study elucidates the molecular mechanisms driving osteoarthritis (OA) by focusing on the transcription factor PU.1's role in synovial cells, specifically macrophages and fibroblast-like synoviocytes (FLS). Analyzing OA-related synovial gene expression from the GEO database highlighted immune regulation pathways in OA. Using protein-protein interaction and the JASPAR database, we pinpointed essential genes in OA development. Synovial tissues from OA patients and controls revealed pronounced PU.1 and its target CSF1R presence. In a surgically induced OA mouse model with PU.1 and CSF1R knockdown, ChIP assays confirmed PU.1's binding to the CSF1R promoter. Dual luciferase reporter assays and immunohistochemistry validated PU.1's regulatory impact on CSF1R transcription. Combined analysis of microarrays GSE55235 and GSE206848 showed heightened PU.1 expression in OA, associated with immune regulation in macrophages. In vitro findings aligned with in vivo results, emphasizing PU.1's influence on macrophage polarization and FLS-induced inflammation. PU.1's direct activation of CSF1R transcription underpins its key role in OA progression. This research offers insights into OA's molecular basis, suggesting potential therapeutic targets.

Similarities and differences between osteoarthritis and rheumatoid arthritis: insights from Mendelian randomization and transcriptome analysis.

BACKGROUND: Osteoarthritis (OA) and rheumatoid arthritis (RA) are often difficult to distinguish in the early stage of the disease. The purpose of this study was to explore the similarities and differences between the two diseases through Mendelian randomization (MR) and transcriptome analysis. METHODS: We first performed a correlation analysis of phenotypic data from genome-wide association studies (GWAS) of OA and RA. Then, we performed functional and pathway enrichment of differentially expressed genes in OA, RA, and normal patients. The infiltration of immune cells in arthritis was analyzed according to gene expression. Finally, MR analysis was performed with inflammatory cytokines and immune cells as exposures and arthritis as the outcome. The same and different key cytokines and immune cells were obtained by the two analysis methods. RESULTS: GWAS indicated that there was a genetic correlation between OA and RA. The common function of OA and RA is enriched in their response to cytokines, while the difference is enriched in lymphocyte activation. T cells are the main immune cells that differentiate between OA and RA. MR analysis further revealed that OA is associated with more protective cytokines, and most of the cytokines in RA are pathogenic. In addition, CCR7 on naive CD4 + T cell was positively correlated with OA. SSC-A on CD4 + T cell was negatively correlated with RA, while HLA DR on CD33- HLA DR + was positively correlated with RA. CONCLUSION: Our study demonstrated the similarities and differences of immune inflammation between OA and RA, allowing us to better understand these two diseases.

Association of autoimmune diseases with the occurrence of osteoarthritis: a gene expression and Mendelian randomization study.

Background: Observational studies have indicated a potential association between autoimmune diseases and the occurrence of Osteoarthritis (OA), with an increased risk of mortality among affected patients. However, whether a causal relationship exists between the two remains unknown. Methods: In the Mendelian randomization (MR) study, we accessed exposure Genome-wide association study (GWAS) data from both the MRC Integrative Epidemiology Unit (MRC-IEU) and the FinnGen consortium. GWAS data for OA were obtained from MRC-IEU. We employed univariable, multivariable, and reverse MR analyses to explore potential associations between autoimmune disorders and OA. Additionally, a two-step mediation MR analysis was performed to investigate indirect factors possibly influencing the relationship between autoimmune disorders and OA. Afterward, we conducted an observational analysis to further explore the relationship between autoimmune disease and occurrence as well as of OA using a real-world database (the MIMIC-IV database). Based on public gene expression sequencing data, we further explored the potential shared pathogenesis between autoimmune diseases and OA. Results: In our univariable MR study, we identified five autoimmune diseases that are associated with OA. These include Celiac disease (OR = 1.061, 95% CI = 1.018-1.105, p = 0.005), Crohn's disease (OR = 1.235, 95% CI = 1.149-1.327, p = 9.44E-09), Ankylosing spondylitis (OR = 2.63, 95% CI = 1.21-5.717, p = 0.015), RA (OR = 1.082, 95% CI = 1.034-1.133, p = 0.001), and Ulcerative colitis (OR = 1.175, 95% CI = 1.068-1.294, p = 0.001). In the mediation effect analysis, it was found that there is no correlation between cytokines and autoimmune diseases and OA. Based on transcriptome data analysis, it was found that metabolism-related pathways play a key role in the co-morbidity of autoimmune diseases and OA. Conclusion: Our findings revealed that genes associated with Celiac disease, Crohn's disease, Ankylosing spondylitis, RA, and Ulcerative colitis were independently linked to the development of OA. Furthermore, we conducted an analysis of potential pathogenic genes between these diseases and OA, offering a novel approach for the simultaneous treatment of multiple conditions.

The Effect of Platelet Dose on Outcomes after Platelet Rich Plasma Injections for Musculoskeletal Conditions: A Systematic Review and Meta-Analysis.

PURPOSE OF REVIEW: This study aims to systematically review platelet dosage in platelet rich plasma (PRP) injections for common musculoskeletal conditions. RECENT FINDINGS: Notable heterogeneity exists in the literature regarding platelet dosage. Clinical studies indicate that a higher dosage may lead to improved outcomes concerning pain relief, functional improvement, and chondroprotection in knee osteoarthritis (OA). However, the impact of dosing on other musculoskeletal pathologies remains uncertain. Our investigation identifies a potential dose-response relationship between platelet dose and PRP effectiveness for knee OA treatment, pinpointing an optimal threshold of greater than 10 billion platelets for favorable clinical outcomes. Notably, this effect appears more pronounced for functional outcomes than for pain relief. For other conditions, a lower dosage may suffice, although the existing literature lacks clarity on this matter. PRP dosage may significantly influence treatmentoutcomes, particularly in knee OA. Further research is warranted to elucidate optimal dosages for varying conditions.

The joint protective function of live- and dead-Lactobacillus plantarum GKD7 on anterior cruciate ligament transection induces osteoarthritis.

Osteoarthritis (OA) is a chronic inflammatory disease accompanied by joint pain, bone degradation, and synovial inflammation. Tumor necrosis factor (TNF)-α and interleukin (IL)-1ß play key roles in chronic inflammation, and matrix metalloproteinase (MMP)3 is the first enzyme released by chondrocytes and synovial cells that promotes MMPs' degrading cartilage matrix (including collage II and aggrecan) function. Using an anterior cruciate ligament transection (ACLT) rat model, Lactobacillus plantarum GKD7 has shown anti-inflammatory and analgesic properties. The present investigation examined the chondroprotective effects of several dosages and formulas of GKD7 on rats in an ACLT-induced OA model. The findings indicate that oral treatment with both live-GKD7 (GKD7-L) and dead-GKD7 (GKD7-D), along with celecoxib (positive control), all reduce post-ACLT pain and inflammation in OA joints. Subsequently, the immunohistochemical staining results demonstrate that following GKD7-L and GKD7-D treatment, there was a reversal of the degradation of collagen II and aggrecan, as well as a decrease in the expression of IL-1ß and TNF-α on the synovial tissue and MMP3 on the cartilage. Accordingly, our findings imply that the treatment of both GKD7-L and GKD7-D has chondroprotective and analgesic effects on the OA rat model, and that celecoxib and GKD7-L at dosages (100 mg/kg) have comparable therapeutic benefits. As a result, we propose that both GKD7-L and GKD7-D are helpful supplements for OA management.

Decisive gene strategy on osteoarthritis: a comprehensive whole-literature based approach for conclusive gene targets.

BACKGROUND: Previous meta-analyses only examined the association between single or several gene polymorphisms and osteoarthritis (OA), whereas no studies have concluded that there are existing all gene loci that associate with OA. OBJECTIVE: To assess whether a definite conclusion of the association between the gene loci and OA can be drawn. METHODS: Decisive gene strategy (DGS), a literature-based approach, was used to search PubMed, Embase, and Cochrane databases for all meta-analyses that associated gene polymorphisms and OA. Trial Sequential Analysis (TSA) examined the sufficiency of the cumulative sample size. Finally, we assessed the importance of gene loci in OA based on whether there were enough sample sizes and the heterogeneity of the literatures with I2 value. RESULTS: After excluding 179 irrelevant publications, 80 meta-analysis papers were recruited. Among Caucasians, SMAD3 rs12901499 (OR = 1.20, 95% CI: 1.12-1.29) was a risk factor with validation of sufficient sample sizes through TSA model. Among Asians, there were 3 gene loci risk factors with validation of sufficient sample sizes through TSA model: ESR1 rs2228480, SMAD3 rs12901499, and MMP-1 rs1799750 (OR = 1.35, 95% CI: 1.08-1.69; OR = 1.34, 95% CI: 1.07-1.69; OR = 1.43, 95% CI: 1.18-1.74, respectively). Besides, 3 gene loci, DVWA rs7639618, GDF5 rs143383, and VDR rs7975232 (OR = 0.78, 95% CI: 0.67-0.90; OR = 0.74, 95% CI: 0.67-0.81; OR = 0.56, 95% CI: 0.35-0.90, respectively) were identified as protective factors through TSA model. CONCLUSIONS: We used DGS to identify conclusive gene loci associated with OA. These findings provide implications of precision medicine in OA and may potentially advance genetic therapy.

The Exosomes of Stem Cells from Human Exfoliated Deciduous Teeth Suppress Inflammation in Osteoarthritis.

Hyaluronic acid injection is commonly used clinically to slow down the development of osteoarthritis (OA). A newly developed therapeutic method is to implant chondrocytes/stem cells to regenerate cartilage in the body. The curative effect of stem cell therapy has been proven to come from the paracrine of stem cells. In this study, exosomes secreted by stem cells from human exfoliated deciduous teeth (SHED) and hyaluronic acid were used individually to evaluate the therapeutic effect in slowing down OA. SHED was cultured in a serum-free medium for three days, and the supernatant was collected and then centrifuged with a speed difference to obtain exosomes containing CD9 and CD63 markers, with an average particle size of 154.1 nm. SW1353 cells were stimulated with IL-1ß to produce the inflammatory characteristics of OA and then treated with 40 µg/mL exosomes and hyaluronic acid individually. The results showed that the exosomes successfully inhibited the pro-inflammatory factors, including TNF-α, IL-6, iNOS, NO, COX-2 and PGE2, induced by IL-1ß and the degrading enzyme of the extrachondral matrix (MMP-13). Collagen II and ACAN, the main components of the extrachondral matrix, were also increased by 1.76-fold and 2.98-fold, respectively, after treatment, which were similar to that of the normal joints. The effect can be attributed to the partial mediation of SHED exosomes to the NF-κB pathway, and the ability of exosomes to inhibit OA is found not inferior to that of hyaluronic acid.

Mapping the Research Landscape of Intra-Articular Knee Injections: A Bibliometric Analysis Using the Scopus Database.

Intraarticular injection of osteoarthritis knee is one of the treatment options for pain management and delays the need for knee surgery. Various materials have been promoted for the procedure, ranging from corticosteroid to viscosupplement to the more recent autologous biological materials. Despite the increasing attention and interest in regard to the material selection, efficacy, safety, and effect of this intervention, a comprehensive bibliometric analysis using the Scopus database has yet to be conducted. In this bibliometric analysis, we reviewed the Scopus database from 2003 to 2023 to investigate the literature on intraarticular injection for the treatment of knee osteoarthritis. A total of 1,318 articles that satisfied the selection criteria were included in this review. The trend of intervention shows changes since 2006, with corticosteroid injection and hyaluronic acid as the main topics of publication before 2006. However, starting in 2010, there has been a noticeable shift towards biological agents, such as plasma-rich proteins, and autologous materials, including marrow aspiration and stromal vascular fraction. This shift reflects the increasing interest in regenerative medicine and the potential of these newer therapies to provide improved outcomes. The overwhelming majority of the articles were authored by researchers and clinicians from across European countries, the United States of America (USA), and Australia. Similarly, most of the articles with the highest number of citations were authored by researchers and clinicians from these regions. This comprehensive bibliometric analysis using Scopus in the domain of intraarticular injection has the potential to act as a roadmap for researchers, clinicians, and policymakers, facilitating informed decision-making, promoting collaborative initiatives, and guiding the development of future studies to further advance the options of knee intraarticular injection, specifically in the management of knee osteoarthritis.

The design of a sample rapid magnetic resonance imaging (MRI) acquisition protocol supporting assessment of multiple articular tissues and pathologies in knee osteoarthritis.

Objective: This expert opinion paper proposes a design for a state-of-the-art magnetic resonance image (MRI) acquisition protocol for knee osteoarthritis clinical trials in early and advanced disease. Semi-quantitative and quantitative imaging endpoints are supported, partly amendable to automated analysis. Several (peri-) articular tissues and pathologies are covered, including synovitis. Method: A PubMed literature search was conducted, with focus on the past 5 years. Further, osteoarthritis imaging experts provided input. Specific MRI sequences, orientations, spatial resolutions and parameter settings were identified to align with study goals. We strived for implementation on standard clinical scanner hardware, with a net acquisition time ≤30 â€‹min. Results: Short- and long-term longitudinal MRIs should be obtained at ≥1.5T, if possible without hardware changes during the study. We suggest a series of gradient- and spin-echo-sequences, supporting MOAKS, quantitative analysis of cartilage morphology and T2, and non-contrast-enhanced depiction of synovitis. These sequences should be properly aligned and positioned using localizer images. One of the sequences may be repeated in each participant (re-test), optimally at baseline and follow-up, to estimate within-study precision. All images should be checked for quality and protocol-adherence as soon as possible after acquisition. Alternative approaches are suggested that expand on the structural endpoints presented. Conclusions: We aim to bridge the gap between technical MRI acquisition guides and the wealth of imaging literature, proposing a balance between image acquisition efficiency (time), safety, and technical/methodological diversity. This approach may entertain scientific innovation on tissue structure and composition assessment in clinical trials on disease modification of knee osteoarthritis.

Comparison of Six-Week, Three-Month, and One-Year Postoperative Clinical Results of Kinematic and Mechanical Alignment in Primary Medial Pivot Total Knee Arthroplasty.

BACKGROUND: Total knee replacement (TKR) is a common surgical solution for severe osteoarthritis. Kinematic alignment (KA) and mechanical alignment (MA) are two popular techniques. There is ongoing debate over the optimal method, influenced by varying long-term results and a scarcity of data on short-term postoperative outcomes. Early evaluation of these techniques is vital for improving rehabilitation outcomes and ensuring patient satisfaction.  Methods: This study retrospectively analyzed outcomes from 71 KA-TKRs and 85 MA-TKRs performed between 2019 and 2021. Knee flexion, visual analog scale (VAS) scores, EuroQol-5d (EQ-5d) quality of life measures, and dependence on walking aids were evaluated. Evaluations were conducted at baseline, six-weeks, three-months, and 12-months postoperatively using two-sample t-tests for continuous data and Pearson's chi-squared test for categorical data. RESULTS: At six-weeks and three-months postoperatively, the KA group exhibited significantly better outcomes in knee flexion (98.6° vs. 90.2° at six-weeks; 114.7° vs. 94.2° at three-months), pain management, and reduced walking aids compared to the MA group. By 12-months, these differences were no longer significant, with both groups showing comparable results in knee flexion, pain scores, and patient-reported outcomes.  Conclusion: KA offers substantial short-term advantages over MA for pain relief, increased knee flexion, and independence from walking aids. However, these benefits do not persist at one-year post-surgery, indicating a convergence of outcomes between the two techniques. Larger studies with extended follow-ups are required to determine the long-term implications of these alignment strategies.

The impact of metabolic syndrome on clinical outcomes following total knee arthroplasty in osteoarthritis patients.

Background: Metabolic syndrome (MetS) is a combination of interconnected conditions, including insulin resistance, abdominal obesity, high blood pressure, and abnormal blood lipid levels. The objective of this research was to investigate the impact of MetS on the quality of life and clinical outcomes following total knee arthroplasty (TKA) in patients with osteoarthritis (OA). Methods: A retrospective descriptive study was conducted to enroll OA patients who underwent primary TKA at Zhongda Hospital, Southeast University from January 2015 to August 2019. A total of 83 OA patients who did and 144 (MetS group) who did not have MetS (non-MetS group) were included. An analysis was conducted on the patient's clinical data. Results: The two groups had similar results in terms of lengths of stay (P=0.93), hospital costs (P=0.24), and overall complication rates (P=0.99). There was no significant difference in the average erythrocyte sedimentation rate and C-reactive protein levels between the groups. However, the MetS group exhibited notably lower Hospital for Special Surgery knee scores and Short Form [36] health survey (SF-36) scores compared to the non-MetS group (both P>0.05) during the one-year follow-up period. Conclusions: OA patients who have MetS had significantly worse knee joint function and quality of life after TKA. There are certain constraints in the current research. First, it belongs to a single-center retrospective study. Further study will be necessary to determine the generality of this conclusion. Second, this study is retrospective, and the number of patients included is not large. Third, due to the diverse clinical groups in our hospital, it is challenging to comprehensively document all the clinical data of the patients involved in this study. Forth, this study did not compare the preoperative differences between the two groups, as well as analyze the postoperative improvement changes in depth. We will compare the preoperative and postoperative differences between the two groups in more depth in future large sample studies.

Potential use of stem cell therapies for treating osteoarthritis and rheumatoid arthritis.

Arthritis, defined as a chronic inflammation often accompanied by swelling of one or more joints, encompasses more than 100 conditions that affect the joints, tissues around them as well as other connective tissues. This condition causes severe discomfort compromising the quality of life drastically, and thereby inflicts severe financial and social impact on the people affected. The incidence rate of arthritis is increasing all around the globe including the United States every year. In general, osteoarthritis (OA) affects more people in comparison to rheumatoid arthritis (RA). In the USA itself, more than 14 million people are affected by OA in comparison to 1.4 million people suffering from RA. In both conditions, elevated levels of proinflammatory cytokines have been recorded, this incidence generally precedes the cartilage degradation observed in the patients. The use of mesenchymal stem cells (MSCs) has proven to be a safe and efficient therapeutic option for treating many inflammation-rooted pathological conditions. Evidence suggests that MSCs down-regulate the effects of proinflammatory cytokines including tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-1B, IL-2, and IL-17, and help restore the functions of immune cells. In addition, these cells promote the polarization of M2 phenotype macrophages, thus contributing to the suppression of the inflammatory process and consequentially to cartilage regeneration. Preclinical and clinical trials have proven the safety and effectiveness of this therapy, supported by the fact that these do not provoke any host immune response, and their influence on the cytokine profiles. An attempt to survey the results of stem cell therapy for treating arthritis has been carried out in this review.

Utilising Discriminant Function Analysis (DFA) for Classifying Osteoarthritis (OA) Patients and Volunteers Based on Biomarker Concentration.

Osteoarthritis (OA) is a degenerative joint disease characterised by the breakdown of cartilage, causing pain, stiffness, and limited movement. Early diagnosis is crucial for effective management but remains challenging due to non-specific early symptoms. This study explores the application of Discriminant Function Analysis (DFA) to classify OA patients and healthy volunteers based on biomarker concentrations of Interleukin-6 (IL-6), Tumour necrosis factor-alpha (TNF-α), and Myeloperoxidase (MPO). DFA was employed to analyse biomarker data from 86 participants (58 patients, 28 volunteers) to evaluate the discriminatory power of these biomarkers in predicting OA. Significant differences were observed in MPO and TNF-α levels between groups, while IL-6 did not show a significant distinction. The iterative classification process improved model assumptions and classification accuracy, achieving a pre-classification accuracy of 71.8%, which adjusted to 57.1% post-classification. The results highlight DFA's potential in OA diagnosis, suggesting its utility in managing complex data and aiding personalised treatment strategies. The study underscores the need for larger sample sizes and additional biomarkers to enhance diagnostic robustness and provides a foundation for integrating DFA into clinical practice for early OA detection.

Multiscale-temporal Feature Extraction and boundary confusion alleviation for VAG-based fine-grained multi-grade osteoarthritis deterioration monitoring.

BACKGROUND AND OBJECTIVE: Multi-grade osteoarthritis (OA) deterioration monitoring in the daily paradigm using Vibroarthrography (VAG) is very challenging due to two difficulties: (1) the composition of VAG signals is complex in the daily paradigm where friction is intensified because of weight-bearing movements. (2) VAG signal samples near the decision boundary of adjacent deterioration grades are easy to be misclassified. The majority of existing works only focus on the binary classification of OA, providing inadequate assistance in instructing physicians to develop treatment plans based on the presence or absence of OA. Thus, we propose a novel framework for fine-grained multi-grade OA deterioration monitoring in the daily paradigm. METHODS: We propose an end-to-end deep learning framework termed Fine-grained Multi-grade OA Deterioration Monitor (FMOADM), which consists of Multiscale-temporal Feature Extraction (MTFE) and Confusion-Free Master-Slave (CF-MS) Classification. Specifically, MTFE is adopted to extract multiscale-temporal discriminative features from the complicated VAG signals. And center loss is introduced by CF-MS to alleviate confusion at the boundary of adjacent deterioration grades in the feature space. Meanwhile, a master-slave structure is proposed for further fine-grained classification, where the master classifier integrates a channel attention mechanism and the slave classifier is designed to update MTFE parameters. As a result, the proposed method ensures fine-grained multi-grade OA monitoring performance via multiscale-temporal discriminative features and boundary confusion alleviation. RESULTS: Experimental results on the VAG-OA dataset demonstrate that our framework outperforms counterpart methods in the daily paradigm. The proposed framework achieved 78% in precision, obtaining an 8% improvement over the state-of-the-art method. CONCLUSION: The proposed framework benefits efficient multi-grade OA deterioration monitoring, empowering physicians to develop treatment plans based on fine-grained monitoring results. It takes knee joint health monitoring in daily activities a step further toward feasible.

Characterizing mitochondrial features in osteoarthritis through integrative multi-omics and machine learning analysis.

Purpose: Osteoarthritis (OA) stands as the most prevalent joint disorder. Mitochondrial dysfunction has been linked to the pathogenesis of OA. The main goal of this study is to uncover the pivotal role of mitochondria in the mechanisms driving OA development. Materials and methods: We acquired seven bulk RNA-seq datasets from the Gene Expression Omnibus (GEO) database and examined the expression levels of differentially expressed genes related to mitochondria in OA. We utilized single-sample gene set enrichment analysis (ssGSEA), gene set enrichment analysis (GSEA), and weighted gene co-expression network analysis (WGCNA) analyses to explore the functional mechanisms associated with these genes. Seven machine learning algorithms were utilized to identify hub mitochondria-related genes and develop a predictive model. Further analyses included pathway enrichment, immune infiltration, gene-disease relationships, and mRNA-miRNA network construction based on these hub mitochondria-related genes. genome-wide association studies (GWAS) analysis was performed using the Gene Atlas database. GSEA, gene set variation analysis (GSVA), protein pathway analysis, and WGCNA were employed to investigate relevant pathways in subtypes. The Harmonizome database was employed to analyze the expression of hub mitochondria-related genes across various human tissues. Single-cell data analysis was conducted to examine patterns of gene expression distribution and pseudo-temporal changes. Additionally, The real-time polymerase chain reaction (RT-PCR) was used to validate the expression of these hub mitochondria-related genes. Results: In OA, the mitochondria-related pathway was significantly activated. Nine hub mitochondria-related genes (SIRT4, DNAJC15, NFS1, FKBP8, SLC25A37, CARS2, MTHFD2, ETFDH, and PDK4) were identified. They constructed predictive models with good ability to predict OA. These genes are primarily associated with macrophages. Unsupervised consensus clustering identified two mitochondria-associated isoforms that are primarily associated with metabolism. Single-cell analysis showed that they were all expressed in single cells and varied with cell differentiation. RT-PCR showed that they were all significantly expressed in OA. Conclusion: SIRT4, DNAJC15, NFS1, FKBP8, SLC25A37, CARS2, MTHFD2, ETFDH, and PDK4 are potential mitochondrial target genes for studying OA. The classification of mitochondria-associated isoforms could help to personalize treatment for OA patients.

Intra-articular injection of modified citrus pectin and hyaluronate gel induces synergistic effects in treating osteoarthritis.

We previously found that modified citrus pectin (MCP), an inhibitor of pro-inflammatory factor Galectin-3 (Gal-3), has significant anti-inflammatory and chondroprotective effects. In this study, a hyaluronate (HA) gel-based sustained release system of MCP (MCP-HA) was developed as an anti-inflammatory agent for chronic inflammation for osteoarthritis (OA) treatment. The MCP-HA gel was injected into the knee joint cavities of OA rabbit models induced by anterior cruciate ligament transection (ACLT) or modified Hulth method once a week for five weeks. We found that MCP-HA could improve the symptoms and signs of OA, protect articular cartilage from degeneration, suppress synovial inflammation, and therefore alleviate OA progression. Proteomic analysis of the synovial fluid obtained from the knee joints of OA rabbits revealed that MCP-HA synergistically regulated the levels of multiple inflammatory mediators and proteins involved in metabolic pathways. Taken together, our results demonstrate that the MCP-HA shows a synergistic effect of HA and MCP by modulating both inflammation and metabolic processes, thereby alleviating OA progression. The MCP-HA sustained release system has promising potential for long-term use in OA treatment.

Removal of the infrapatellar fat pad and associated synovium benefits female guinea pigs in the Dunkin Hartley model of idiopathic osteoarthritis.

Background: Several tissues contribute to the onset and advancement of knee osteoarthritis (OA). One tissue type that is worthy of closer evaluation, particularly in the context of sex, is the infrapatellar fat pad (IFP). We previously demonstrated that removal of the IFP had short-term beneficial effects for a cohort of male Dunkin-Hartley guinea pigs. The present project was designed to elucidate the influence of IFP removal in females of this OA-prone strain. It was hypothesized that resection of the IFP would reduce the development of OA in knees of a rodent model predisposed to the disease. Methods: Female guinea pigs (n=16) were acquired at an age of 2.5 months. Surgical removal of the IFP and associated synovium complex (IFP/SC) was executed at 3 months of age. One knee had the IFP/SC resected; a comparable sham surgery was performed on the contralateral knee. All animals were subjected to voluntary enclosure monitoring and dynamic weight-bearing, as well as compulsory treadmill-based gait analysis monthly; baseline data was collected prior to surgery. Guinea pigs were euthanized at 7 months. Knees from eight animals were evaluated via histology, mRNA expression, and immunohistochemistry (IHC); knees from the remaining eight animals were allocated to microcomputed tomography (microCT), biomechanical analyses (whole joint testing and indentation relaxation testing), and atomic absorption spectroscopy (AAS). Results: Fibrous connective tissue (FCT) replaced the IFP/SC. Mobility/gait data indicated that unilateral IFP/SC removal did not affect bilateral hindlimb movement. MicroCT demonstrated that osteophytes were not a significant feature of OA in this sex; however, trabecular thickness (TbTh) in medial femorae decreased in knees containing the FCT. Histopathology scores were predominantly influenced by changes in the lateral tibia, which demonstrated that histologic signs of OA were increased in knees containing the native IFP/SC versus those with the FCT. Similarly, indentation testing demonstrated higher instantaneous and equilibrium moduli in the lateral tibial articular cartilage of control knees with native IFPs. AAS of multiple tissue types associated with the knee revealed that zinc was the major trace element influenced by removal of the IFP/SC. Conclusions: Our data suggest that the IFP/SC is a significant component driving knee OA in female guinea pigs and that resection of this tissue prior to disease has short-term benefits. Specifically, the formation of the FCT in place of the native tissue resulted in decreased cartilage-related OA changes, as demonstrated by reduced Osteoarthritis Research Society International (OARSI) histology scores, as well as changes in transcript, protein, and cartilage indentation analyses. Importantly, this model provides evidence that sex needs to be considered when investigating responses and associated mechanisms seen with this intervention.

Role of Autologous Micro-Fragmented Adipose Tissue in Osteoarthritis Treatment.

Osteoarthritis (OA) is the most common complex musculoskeletal disorder, resulting from the degeneration of the articular cartilage and characterized by joint pain and dysfunction that culminate in progressive articular cartilage loss. We present our experience in the management of hip and knee OA by means of the intra-articular injection of fat micrograft, describing our approach, which was developed from the belief in the powerful reparative effect of autologous fat graft on damaged tissue, as well as its natural lubricating effect on the joints. Inclusion criteria were as follows: men and women, aged 20 to 80 years, that referred articular pain of the hips and/or knees, showing initial-stage degenerative OA. From October 2018 to July 2023, a total of 250 patients underwent treatment with the Sefficare® device (SEFFILINE srl, Bologna, Italy). The Superficial Enhanced Fluid Fat Injection device was used to perform autologous regenerative treatments in a safe, standardized, easy, and effective way on 160 women, 64%, and 90 men, 36%. A total of 190 procedures (76%) involved the knees, with 20 patients who were bilaterally treated, while 60 procedures, all unilateral, involved the hips (24%). The mean age at treatment was 52.4 years. Before treatment, each patient had undergone X-rays and Magnetic Resonance Imaging (MRI) of the painful hip/knee to evaluate and grade the articular OA. Postoperatively, each patient was assessed after one, three, six, and twelve months. The donor site postoperative course was uneventful other than minimal discomfort. Clinically, the ROM (range of motion) of the treated knee/hip increased an average of 10 degrees 3 months after treatment, but the stiffness was reduced, as reported by the patients. The VAS (Visual Analog Scale) was submitted at 3, 6, and 12 months, demonstrating a progressive reduction of pain, with the best score obtained at six months postoperatively. In total, 85% of patients were satisfied one year after treatment, with a considerable improvement in pain and quality of life. The satisfactory outcome of this minimally invasive procedure indicates that the intra-articular injection of fat micrograft can replace or considerably delay the need for the classical major joint replacement surgery, thanks to its impact on the quality of life of patients and financial cost.

Heme oxygenase 1 linked to inactivation of subchondral osteoclasts in osteoarthritis. / è¡€çº¢ç´ åŠ æ°§é ¶1ä¸Žéª¨å ³èŠ‚ç‚Žè½¯éª¨ä¸‹ç ´éª¨ç»†èƒžå¤±æ´»çš„ç›¸å ³ç ”ç©¶.

Osteoarthritis (OA) is a chronic progressive osteoarthropathy in the elderly. Osteoclast activation plays a crucial role in the occurrence of subchondral bone loss in early OA. However, the specific mechanism of osteoclast differentiation in OA remains unclear. In our study, gene expression profiles related to OA disease progression and osteoclast activation were screened from the Gene Expression Omnibus (GEO) repository. GEO2R and Funrich analysis tools were employed to find differentially expressed genes (DEGs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses demonstrated that chemical carcinogenesis, reactive oxygen species (ROS), and response to oxidative stress were mainly involved in osteoclast differentiation in OA subchondral bone. Furthermore, fourteen DEGs that are associated with oxidative stress were identified. The first ranked differential gene, heme oxygenase 1 (HMOX1), was selected for further validation. Related results showed that osteoclast activation in the pathogenesis of OA subchondral bone is accompanied by the downregulation of HMOX1. Carnosol was revealed to inhibit osteoclastogenesis by targeting HMOX1 and upregulating the expression of antioxidant protein in vitro. Meanwhile, carnosol was found to alleviate the severity of OA by inhibiting the activation of subchondral osteoclasts in vivo. Our research indicated that the activation of osteoclasts due to subchondral bone redox dysplasia may serve as a significant pathway for the advancement of OA. Targeting HMOX1 in subchondral osteoclasts may offer novel insights for the treatment of early OA.