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Scientific Reports May 2024Knee osteoarthritis (OA) diagnosis is based on symptoms, assessed through questionnaires such as the WOMAC. However, the inconsistency of pain recording and the...
Characterization of clinical data for patient stratification in moderate osteoarthritis with support vector machines, regulatory network models, and verification against osteoarthritis Initiative data.
Knee osteoarthritis (OA) diagnosis is based on symptoms, assessed through questionnaires such as the WOMAC. However, the inconsistency of pain recording and the discrepancy between joint phenotype and symptoms highlight the need for objective biomarkers in knee OA diagnosis. To this end, we study relationships among clinical and molecular data in a cohort of women (n = 51) with Kellgren-Lawrence grade 2-3 knee OA through a Support Vector Machine (SVM) and a regulation network model. Clinical descriptors (i.e., pain catastrophism, depression, functionality, joint pain, rigidity, sensitization and synovitis) are used to classify patients. A Youden's test is performed for each classifier to determine optimal binarization thresholds for the descriptors. Thresholds are tested against patient stratification according to baseline WOMAC data from the Osteoarthritis Initiative, and the mean accuracy is 0.97. For our cohort, the data used as SVM inputs are knee OA descriptors, synovial fluid proteomic measurements (n = 25), and transcription factor activation obtained from regulatory network model stimulated with the synovial fluid measurements. The relative weights after classification reflect input importance. The performance of each classifier is evaluated through ROC-AUC analysis. The best classifier with clinical data is pain catastrophism (AUC = 0.9), highly influenced by funcionality and pain sensetization, suggesting that kinesophobia is involved in pain perception. With synovial fluid proteins used as input, leptin strongly influences every classifier, suggesting the importance of low-grade inflammation. When transcription factors are used, the mean AUC is limited to 0.608, which can be related to the pleomorphic behaviour of osteoarthritic chondrocytes. Nevertheless, funcionality has an AUC of 0.7 with a decisive importance of FOXO downregulation. Though larger and longitudinal cohorts are needed, this unique combination of SVM and regulatory network model shall help to stratify knee OA patients more objectively.
Topics: Humans; Female; Osteoarthritis, Knee; Support Vector Machine; Middle Aged; Aged; Gene Regulatory Networks; Biomarkers; Synovial Fluid; Proteomics
PubMed: 38782951
DOI: 10.1038/s41598-024-62212-x -
Acta Ortopedica Mexicana 2024metacarpophalangeal dislocations of the thumb are not very frequent injuries, it is necessary to know the anatomy of the region to know possible causes of interposition...
INTRODUCTION
metacarpophalangeal dislocations of the thumb are not very frequent injuries, it is necessary to know the anatomy of the region to know possible causes of interposition that prevent a closed reduction of this pathology.
CASE PRESENTATION
we present the case of a 75-year-old woman with a post-traumatic metacarpophalangeal dislocation of the thumb that required open reduction and surgical repair. In this procedure, we performed reduction of the dislocation, mobilization of the interposed structures, repair of the capsule and reinsertion of the ulnar collateral ligament. The early mobilization protocol helped to obtain very good results.
CONCLUSION
it is imperative to consider possible associated injuries during the acute phase to achieve optimal short, medium, and long-term outcomes for our patients. A comprehensive and proactive approach to diagnosis and treatment is vital in effectively addressing this pathology and minimizing its potential sequelae.
Topics: Humans; Metacarpophalangeal Joint; Female; Joint Dislocations; Aged; Thumb; Collateral Ligament, Ulnar
PubMed: 38782479
DOI: No ID Found -
Frontiers in Immunology 2024
Topics: Arthritis, Rheumatoid; Humans; Fibroblasts; Synoviocytes; Immunomodulation; Animals; Synovial Membrane
PubMed: 38779670
DOI: 10.3389/fimmu.2024.1415672 -
Cureus Apr 2024Hallux valgus (HV) is a relatively frequent disease caused by a complicated structural malformation of the primary ray. The bunion or middle projection generated by the... (Review)
Review
Hallux valgus (HV) is a relatively frequent disease caused by a complicated structural malformation of the primary ray. The bunion or middle projection generated by the hallux's lateral displacement and pronation is merely one element of the three-dimensional abnormality. HV may trigger severe discomfort and affect joint kinematics. The specific kinematic cause is still unknown. Female age, gender, restrictive footwear, and heritage are risk indicators. HV frequently coexists along metatarsal adducts, equines contracture, hammertoe imperfection, and pes planus. HV is a frequent foot ailment with multiple, complicated, unknown etiology and course. HV has a preference for females. It is an ongoing condition for which there is no known treatment to reduce or prevent improvement. Fibrodysplasia ossificans progressiva (FOP) is distinguished by hereditary symmetrical HV deformities or symptoms that begin heterotopic calcification that is either idiopathic or caused by trauma, such as subcutaneous immunizations. Localized heterotopic calcification may be preceded by aggravating, recurring soft-tissue enlargements (flare-ups). Heterotopic calcification may happen anywhere; however, it most commonly impacts locations near the axial bone structure during the early/mild phases until advancing to the appendicular skeleton. As an effect of calcification affecting the flexibility of the joints, it might cause limitations in motion. The initial line of therapy focuses on non-surgical methods including night splinting, orthotics, and larger shoes. The next suggested line of action is surgical intervention if conservative therapy fails. Patients have good postoperative tolerance, and bone union often happens six to seven weeks after surgery. Stretching exercises help to restore function by extending shortened soft tissue and restoring range of motion (ROM). The goal of joint mobilization, a form of manual treatment method, is to extend the ligament, the soft tissue surrounding the limited joint, and the restricting joint capsule by applying modest amplitude passive movement to the joint components.
PubMed: 38779237
DOI: 10.7759/cureus.58750 -
F1000Research 2023Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by autoantibody production and synovial membrane damage. It significantly impairs overall... (Randomized Controlled Trial)
Randomized Controlled Trial
Role of specialized pro-resolving mediators on inflammation, cardiometabolic health, disease progression, and quality of life after omega-3 PUFA supplementation and aerobic exercise training in individuals with rheumatoid arthritis: a randomized 16-week, placebo-controlled interventional trial.
Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by autoantibody production and synovial membrane damage. It significantly impairs overall function and quality of life. Consumption of omega-3 (n-3) polyunsaturated fatty acids (PUFAs) and regular aerobic exercise (AEx) training are reported to have positive effects on the progression of RA. However, the mechanisms behind these benefits are still inconclusive. This study protocol will investigate the effects of n-3 PUFA supplementation and AEx training on disease progression, cardiometabolic health, and quality of life, and their association with the plasma and synovial fluid levels of specialized pro-resolving mediators (SPMs) in subjects with RA. The study consists of a 16-week intervention period, during which participants will be randomly assigned in a double-blinded manner to one of four groups: placebo control (PLA), PLA+AEx, n-3, or n-3+AEx. The PLA groups will be given a gelatin-filled capsule, while the n-3 groups will be given n-3 PUFAs equivalent to 2.5 g/d of docosahexaenoic acid and 0.5 g/d of eicosapentaenoic acid. The AEx groups will perform exercise three times per week on a stationary electronically braked cycle ergometer at 60-70% of their VO2peak for 50-60 minutes. Before and after the intervention, participants will undergo RA-specific and functional measurements, peak aerobic capacity test, and a dietary and physical activity assessment. Venous blood and synovial fluid from the knee joint will be collected. Changes in disease progression, cardiometabolic health, and quality of life, as well as erythrocyte membrane composition to assess n-3 incorporation, SPM levels, inflammatory markers, and gene expression from blood and synovial fluid will be analyzed. The study aims to elucidate the SPMs that regulate the inflammatory gene expression pathways and associate them with the improvements in disease progression, cardiometabolic health, and quality of life after n-3 PUFA supplementation and AEx training. : ClinicalTrials.gov #NCT05945693.
Topics: Humans; Arthritis, Rheumatoid; Fatty Acids, Omega-3; Quality of Life; Dietary Supplements; Disease Progression; Exercise; Inflammation; Double-Blind Method; Male; Female; Middle Aged; Adult
PubMed: 38778807
DOI: 10.12688/f1000research.138392.1 -
Pharmacological Research Jul 2024Current anti-rheumatic drugs are primarily modulating immune cell activation, yet their effectiveness remained suboptimal. Therefore, novel therapeutics targeting...
INTRODUCTION
Current anti-rheumatic drugs are primarily modulating immune cell activation, yet their effectiveness remained suboptimal. Therefore, novel therapeutics targeting alternative mechanisms, such as synovial activation, is urgently needed.
OBJECTIVES
To explore the role of Midline-1 (Mid1) in synovial activation.
METHODS
NOD.Cg-Prkdc Il2rg/SzJ (NSG) mice were used to establish a subcutaneous xenograft model. Wild-type C57BL/6, Mid1, Dpp4, and Mid1Dpp4 mice were used to establish a collagen-induced arthritis model. Cell viability, cell cycle, qPCR and western blotting analysis were used to detect MH7A proliferation, dipeptidyl peptidase-4 (DPP4) and Mid1 levels. Co-immunoprecipitation and proteomic analysis identified the candidate protein of Mid1 substrates. Ubiquitination assays were used to determine DPP4 ubiquitination status.
RESULTS
An increase in Mid1, an E3 ubiquitin ligase, was observed in human RA synovial tissue by GEO dataset analysis, and this elevation was confirmed in a collagen-induced mouse arthritis model. Notably, deletion of Mid1 in a collagen-induced arthritis model completely protected mice from developing arthritis. Subsequent overexpression and knockdown experiments on MH7A, a human synoviocyte cell line, unveiled a previously unrecognized role of Mid1 in synoviocyte proliferation and migration, the key aspects of synovial activation. Co-immunoprecipitation and proteomic analysis identified DPP4 as the most significant candidate of Mid1 substrates. Mechanistically, Mid1 promoted synoviocyte proliferation and migration by inducing ubiquitin-mediated proteasomal degradation of DPP4. DPP4 deficiency led to increased proliferation, migration, and inflammatory cytokine production in MH7A, while reconstitution of DPP4 significantly abolished Mid1-induced augmentation of cell proliferation and activation. Additionally, double knockout model showed that DPP4 deficiency abolished the protective effect of Mid1 defect on arthritis.
CONCLUSION
Overall, our findings suggest that the ubiquitination of DPP4 by Mid1 promotes synovial cell proliferation and invasion, exacerbating synovitis in RA. These results reveal a novel mechanism that controls synovial activation, positioning Mid1 as a promising target for therapeutic intervention in RA.
Topics: Animals; Arthritis, Rheumatoid; Humans; Dipeptidyl Peptidase 4; Arthritis, Experimental; Ubiquitin-Protein Ligases; Mice, Inbred C57BL; Mice; Synovitis; Protein Processing, Post-Translational; Mice, Knockout; Ubiquitination; Ubiquitin; Mice, Inbred NOD; Synovial Membrane; Male; Cell Proliferation; Transcription Factors; Synoviocytes
PubMed: 38777113
DOI: 10.1016/j.phrs.2024.107224 -
The Journal of Bone and Joint Surgery.... Jul 2024➤ No single test has demonstrated absolute accuracy for the diagnosis of periprosthetic joint infection (PJI).➤ Physicians rely on a combination of serological... (Review)
Review
➤ No single test has demonstrated absolute accuracy for the diagnosis of periprosthetic joint infection (PJI).➤ Physicians rely on a combination of serological tests, synovial markers, and clinical findings plus clinical judgment to help to guide preoperative decision-making.➤ Several organizations have proposed criteria for the diagnosis of hip or knee PJI on which we now rely.➤ Given that shoulder arthroplasty has only recently become popular, it is possible that a shoulder-specific definition of PJI will be introduced in the coming years.➤ Although a number of serum and synovial markers have demonstrated high accuracy for the diagnosis of PJI of the hip and knee, further research is needed in order to identify markers that may be more suitable for the diagnosis of shoulder PJI and for the potential development and identification of specific serological tests as screening tools for PJI.
Topics: Humans; Prosthesis-Related Infections; Biomarkers; Algorithms; Synovial Fluid; Shoulder Prosthesis; Arthroplasty, Replacement, Shoulder; Arthroplasty, Replacement, Knee; Knee Prosthesis; Hip Prosthesis; Arthroplasty, Replacement, Hip
PubMed: 38776388
DOI: 10.2106/JBJS.23.00669 -
PloS One 2024To elucidate potential molecular mechanisms differentiating osteoarthritis (OA) and rheumatoid arthritis (RA) through a bioinformatics analysis of differentially...
OBJECTIVE
To elucidate potential molecular mechanisms differentiating osteoarthritis (OA) and rheumatoid arthritis (RA) through a bioinformatics analysis of differentially expressed genes (DEGs) in patient synovial cells, aiming to provide new insights for clinical treatment strategies.
MATERIALS AND METHODS
Gene expression datasets GSE1919, GSE82107, and GSE77298 were downloaded from the Gene Expression Omnibus (GEO) database to serve as the training groups, with GSE55235 being used as the validation dataset. The OA and RA data from the GSE1919 dataset were merged with the standardized data from GSE82107 and GSE77298, followed by batch effect removal to obtain the merged datasets of differential expressed genes (DEGs) for OA and RA. Intersection analysis was conducted on the DEGs between the two conditions to identify commonly upregulated and downregulated DEGs. Enrichment analysis was then performed on these common co-expressed DEGs, and a protein-protein interaction (PPI) network was constructed to identify hub genes. These hub genes were further analyzed using the GENEMANIA online platform and subjected to enrichment analysis. Subsequent validation analysis was conducted using the GSE55235 dataset.
RESULTS
The analysis of differentially expressed genes in the synovial cells from patients with Osteoarthritis (OA) and Rheumatoid Arthritis (RA), compared to a control group (individuals without OA or RA), revealed significant changes in gene expression patterns. Specifically, the genes APOD, FASN, and SCD were observed to have lower expression levels in the synovial cells of both OA and RA patients, indicating downregulation within the pathological context of these diseases. In contrast, the SDC1 gene was found to be upregulated, displaying higher expression levels in the synovial cells of OA and RA patients compared to normal controls.Additionally, a noteworthy observation was the downregulation of the transcription factor PPARG in the synovial cells of patients with OA and RA. The decrease in expression levels of PPARG further validates the alteration in lipid metabolism and inflammatory processes associated with the pathogenesis of OA and RA. These findings underscore the significance of these genes and the transcription factor not only as biomarkers for differential diagnosis between OA and RA but also as potential targets for therapeutic interventions aimed at modulating their expression to counteract disease progression.
CONCLUSION
The outcomes of this investigation reveal the existence of potentially shared molecular mechanisms within Osteoarthritis (OA) and Rheumatoid Arthritis (RA). The identification of APOD, FASN, SDC1, TNFSF11 as key target genes, along with their downstream transcription factor PPARG, highlights common potential factors implicated in both diseases. A deeper examination and exploration of these findings could pave the way for new candidate targets and directions in therapeutic research aimed at treating both OA and RA. This study underscores the significance of leveraging bioinformatics approaches to unravel complex disease mechanisms, offering a promising avenue for the development of more effective and targeted treatments.
Topics: Arthritis, Rheumatoid; Humans; Osteoarthritis; Gene Expression Profiling; Protein Interaction Maps; Synovial Membrane; Computational Biology; Gene Regulatory Networks; Gene Expression Regulation; Databases, Genetic
PubMed: 38771826
DOI: 10.1371/journal.pone.0303506 -
Journal of Orthopaedic Surgery (Hong... 2024The purpose of this study was to investigate the effect of 3D-printed technology to repair glenoid bone defect on shoulder joint stability. The shoulder joints of 25...
The purpose of this study was to investigate the effect of 3D-printed technology to repair glenoid bone defect on shoulder joint stability. The shoulder joints of 25 male cadavers were tested. The 3D-printed glenoid pad was designed and fabricated. The specimens were divided into 5 groups. Group A: no bone defect and the structure of the glenoid labrum and joint capsule was intact; Group B: Anterior inferior bone defect of the shoulder glenoid; Group C: a pad with a width of 2 mm was installed; Group D: a pad with a width of 4 mm was installed; Group E: a pad with a width of 6 mm was installed. This study measured the distance the humeral head moved forward at the time of glenohumeral dislocation and the maximum load required to dislocate the shoulder. The shoulder joint stability and humerus displacement was significantly lower in groups B and C compared with group A ( < .05). Compared with group A, the stability of the shoulder joint of group D was significantly improved ( < .05). However, there was no significant difference in humerus displacement between groups D and A ( > .05). In addition, compared with group A, shoulder joint stability was significantly increased and humerus displacement was significantly decreased in group E ( < .05). The 3D-printed technology can be used to make the shoulder glenoid pad to perfectly restore the geometric shape of the shoulder glenoid articular surface. Moreover, the 3D-printed pad is 2 mm larger than the normal glenoid width to restore the initial stability of the shoulder joint.
Topics: Humans; Printing, Three-Dimensional; Male; Titanium; Shoulder Joint; Biomechanical Phenomena; Cadaver; Alloys; Joint Instability; Glenoid Cavity; Prosthesis Design
PubMed: 38769768
DOI: 10.1177/10225536241257169 -
Journal of Nanobiotechnology May 2024Osteoarthritis (OA) is a prevalent degenerative joint disorder, marked by the progressive degeneration of joint cartilage, synovial inflammation, and subchondral bone...
BACKGROUND AND AIMS
Osteoarthritis (OA) is a prevalent degenerative joint disorder, marked by the progressive degeneration of joint cartilage, synovial inflammation, and subchondral bone hyperplasia. The synovial tissue plays a pivotal role in cartilage regulation. Exosomes (EXOs), small membrane-bound vesicles released by cells into the extracellular space, are crucial in mediating intercellular communication and facilitating the exchange of information between tissues. Our study aimed to devise a hydrogel microsphere infused with SOD3-enriched exosomes (S-EXOs) to protect cartilage and introduce a novel, effective approach for OA treatment.
MATERIALS AND METHODS
We analyzed single-cell sequencing data from 4247 cells obtained from the GEO database. Techniques such as PCR, Western Blot, immunofluorescence (IF), and assays to measure oxidative stress levels were employed to validate the cartilage-protective properties of the identified key protein, SOD3. In vivo, OA mice received intra-articular injections of S-EXOs bearing hydrogel microspheres, and the effectiveness was assessed using safranine O (S.O) staining and IF.
RESULTS
Single-cell sequencing data analysis suggested that the synovium influences cartilage via the exocrine release of SOD3. Our findings revealed that purified S-EXOs enhanced antioxidant capacity of chondrocytes, and maintained extracellular matrix metabolism stability. The S-EXO group showed a significant reduction in mitoROS and ROS levels by 164.2% (P < 0.0001) and 142.7% (P < 0.0001), respectively, compared to the IL-1β group. Furthermore, the S-EXO group exhibited increased COL II and ACAN levels, with increments of 2.1-fold (P < 0.0001) and 3.1-fold (P < 0.0001), respectively, over the IL-1β group. Additionally, the S-EXO group showed a decrease in MMP13 and ADAMTS5 protein expression by 42.3% (P < 0.0001) and 44.4% (P < 0.0001), respectively. It was found that S-EXO-containing hydrogel microspheres could effectively deliver SOD3 to cartilage and significantly mitigate OA progression. The OARSI score in the S-EXO microsphere group markedly decreased (P < 0.0001) compared to the OA group.
CONCLUSION
The study demonstrated that the S-EXOs secreted by synovial fibroblasts exert a protective effect on chondrocytes, and microspheres laden with S-EXOs offer a promising therapeutic alternative for OA treatment.
Topics: Animals; Osteoarthritis; Exosomes; Mice; Oxidative Stress; Chondrocytes; Humans; Superoxide Dismutase; Synovial Membrane; Male; Disease Progression; Nanoparticles; Mice, Inbred C57BL; Hydrogels; Microspheres; Cartilage, Articular; Extracellular Matrix
PubMed: 38769545
DOI: 10.1186/s12951-024-02538-w