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Journal of Orthopaedic Surgery and... May 2024To investigate the effect and underlying mechanism of umbilical cord blood-mononuclear cells (UCB-MNCs) in treating knee osteoarthritis (KOA) in rabbits.
BACKGROUND
To investigate the effect and underlying mechanism of umbilical cord blood-mononuclear cells (UCB-MNCs) in treating knee osteoarthritis (KOA) in rabbits.
METHODS
A rabbit KOA model was prepared by anterior cruciate ligament transection (ACLT). Fifty New Zealand white rabbits were randomly divided into the control group, model group, sodium hyaluronate (SH) group, platelet-rich plasma (PRP) group and UCB-MNC group. Knee injections were performed once a week for five consecutive weeks. The gross view of the knee joint, morphology of knee cartilage and structural changes in the knee joint were observed on CT scans, and graded by the Lequesne MG behavioral score and the Mankin score. TNF-α and IL-1β levels in the synovial fluid of the knee were measured by the enzyme-linked immunosorbent assay (ELISA). Expression levels of MMP-13 and COL-II in the knee cartilage were detected by Western blotting and qRT-PCR.
RESULTS
The Lequesne MG behavioral score and the Mankin score were significantly higher in the model group than those in the control group (P < 0.05). Rabbits in the SH, PRP and UCB-MNC groups had sequentially lower scores than those in the model group. Imaging features of KOA were more pronounced in the model group than in the remaining groups. CB-MNC significantly relieved KOA, compared to SH and PRP. Significantly higher levels of TNF-α and IL-1β in the synovial fluid of the knee, and up-regulated MMP-13 and down-regulated COL-II in the knee cartilage were detected in the model group than in the control group. These changes were significantly reversed by the treatment with SH, PRP and UCB-MNCs, especially UCB-MNCs.
CONCLUSION
Injections of UCB-MNCs into knees protect the articular cartilage and hinder the progression of KOA in rabbits by improving the local microenvironment at knee joints.
Topics: Animals; Rabbits; Osteoarthritis, Knee; Fetal Blood; Disease Models, Animal; Male; Leukocytes, Mononuclear; Interleukin-1beta; Tumor Necrosis Factor-alpha; Synovial Fluid; Platelet-Rich Plasma; Cord Blood Stem Cell Transplantation; Random Allocation
PubMed: 38811966
DOI: 10.1186/s13018-024-04815-8 -
European Journal of Medical Research May 2024Joint contracture is one of the common diseases clinically, and joint capsule fibrosis is considered to be one of the most important pathological changes of joint...
Joint contracture is one of the common diseases clinically, and joint capsule fibrosis is considered to be one of the most important pathological changes of joint contracture. However, the underlying mechanism of joint capsule fibrosis is still controversial. The present study aims to establish an animal model of knee extending joint contracture in rats, and to investigate the role of hypoxia-mediated pyroptosis in the progression of joint contracture using this animal model. 36 male SD rats were selected, 6 of which were not immobilized and were used as control group, while 30 rats were divided into I-1 group (immobilized for 1 week following 7 weeks of free movement), I-2 group (immobilized for 2 weeks following 6 weeks of free movement), I-4 group (immobilized for 4 weeks following 4 weeks of free movement), I-6 group (immobilized for 6 weeks following 2 weeks of free movement) and I-8 group (immobilized for 8 weeks) according to different immobilizing time. The progression of joint contracture was assessed by the measurement of knee joint range of motion, collagen deposition in joint capsule was examined with Masson staining, protein expression levels of HIF-1α, NLRP3, Caspase-1, GSDMD-N, TGF-β1, α-SMA and p-Smad3 in joint capsule were assessed using western blotting, and the morphological changes of fibroblasts were observed by transmission electron microscopy. The degree of total and arthrogenic contracture progressed from the first week and lasted until the first eight weeks after immobilization. The degree of total and arthrogenic contracture progressed rapidly in the first four weeks after immobilization and then progressed slowly. Masson staining indicated that collagen deposition in joint capsule gradually increased in the first 8 weeks following immobilization. Western blotting analysis showed that the protein levels of HIF-1α continued to increase during the first 8 weeks of immobilization, and the protein levels of pyroptosis-related proteins NLRP3, Caspase-1, GSDMD-N continued to increase in the first 4 weeks after immobilization and then decreased. The protein levels of fibrosis-related proteins TGF-β1, p-Smad3 and α-SMA continued to increase in the first 8 weeks after immobilization. Transmission electron microscopy showed that 4 weeks of immobilization induced cell membrane rupture and cell contents overflow, which further indicated the activation of pyroptosis. Knee extending joint contracture animal model can be established by external immobilization orthosis in rats, and the activation of hypoxia-mediated pyroptosis may play a stimulating role in the process of joint capsule fibrosis and joint contracture.
Topics: Animals; Contracture; Pyroptosis; Rats; Male; Knee Joint; Rats, Sprague-Dawley; Hypoxia-Inducible Factor 1, alpha Subunit; NLR Family, Pyrin Domain-Containing 3 Protein; Hypoxia; Disease Models, Animal; Transforming Growth Factor beta1; Joint Capsule; Range of Motion, Articular; Smad3 Protein
PubMed: 38802976
DOI: 10.1186/s40001-024-01890-9 -
Arthritis Research & Therapy May 2024Psoriatic arthritis (PsA) is an inflammatory arthritis associated with psoriasis. PsA disease involves flares, which are associated with increased joint inflammation and...
BACKGROUND
Psoriatic arthritis (PsA) is an inflammatory arthritis associated with psoriasis. PsA disease involves flares, which are associated with increased joint inflammation and tissue remodeling. There is a need for identifying biomarkers related to PsA disease activity and flares to improve the management of PsA patients and decrease flares. The tissue turnover imbalance that occurs during the inflammatory and fibro-proliferative processes during flares leads to an increased degradation and/or reorganization of the extracellular matrix (ECM), where increased proteolysis plays a key role. Hence, protease-mediated fragments of inflammatory and tissue-remodeling components could be used as markers reflecting flares in PsA patients.
METHODS
A broad panel of protease-mediated biomarkers reflecting inflammation and tissue remodeling was measured in serum and synovial fluid (SF) obtained from PsA patients experiencing flares (acutely swollen joint[s], PsA-flare). In serum, biomarker levels assessed in PsA-flare patients were compared to controls and in early-diagnosed PsA patients not experiencing flares (referred to as PsA without flare). Furthermore, the biomarker levels assessed in SF from PsA-flare patients were compared to the levels in SF of osteoarthritis (OA) patients.
RESULTS
In serum, levels of the PRO-C3 and C3M, reflecting formation and degradation of the interstitial matrix, were found significantly elevated in PsA-flare compared to controls and PsA without flare. The remodeling marker of the basement membrane, PRO-C4, was significantly elevated in PsA-flare compared to PsA without flare. The inflammation and immune cell activity related markers, CRPM, VICM, and CPa9-HNE were significantly elevated in PsA-flare patients compared to controls and PsA without flare. In addition, VICM (AUC = 0.71), CPa9-HNE (AUC = 0.89), CRPM (AUC = 0.76), and PRO-C3 (AUC = 0.86) showed good discriminatory performance for separating PsA-flare from PsA without flare. In SF, the macrophage activity marker, VICM, was significantly elevated whereas the type II collagen formation marker, PRO-C2, was significantly reduced in the PsA-flare compared to OA. The combination of five serum markers reflecting type III and IV collagen degradation (C3M and C4M, respectively), type III and VI collagen formation (PRO-C3 and PRO-C6, respectively), and neutrophil activity (CPa9-HNE) showed an excellent discriminatory performance (AUC = 0.98) for separating PsA-flare from PsA without flares.
CONCLUSIONS
The serum biomarker panel of C3M, C4M, PRO-C3, PRO-C6, and CPa9-HNE reflecting synovitis, enthesitis, and neutrophil activity may serve as novel tool for quantitatively monitoring flares in PsA patients.
Topics: Humans; Arthritis, Psoriatic; Biomarkers; Male; Female; Middle Aged; Adult; Synovial Fluid; Peptide Hydrolases; Inflammation; Aged; Peptides
PubMed: 38802975
DOI: 10.1186/s13075-024-03332-7 -
Scientific Reports May 2024Recently, we found significantly reduced total superoxide dismutase (SOD) activity in the cartilage of patients with end-stage knee osteoarthritis (OA). In this study,...
Recently, we found significantly reduced total superoxide dismutase (SOD) activity in the cartilage of patients with end-stage knee osteoarthritis (OA). In this study, we aimed to evaluate the SOD activity in serum, joint fluid, cartilage, and synovial membrane samples collected from 52 patients with end-stage knee OA who underwent total knee arthroplasty. The relationship between the total SOD activity in each tissue was evaluated using Spearman's rank correlation coefficient. The joint fluid total SOD activity was used as the objective variable, and its association with the serum, cartilage, and synovial total SOD activities was evaluated using multiple linear regression analysis. Univariate analysis revealed that joint fluid total SOD activity was positively correlated with synovial total SOD activity. Multiple linear regression analysis using joint fluid total SOD activity as the objective variable showed a positive association with synovial total SOD activity (β = 0.493, adjusted R = 0.172, P < 0.01). In patients with end-stage knee OA, the state of the synovial total SOD activity is better reflected by the total SOD activity in the joint fluid than that in the cartilage. Joint fluid total SOD activity may serve as a biomarker for the treatment and prevention of synovitis.
Topics: Humans; Osteoarthritis, Knee; Male; Female; Synovial Fluid; Superoxide Dismutase; Synovial Membrane; Aged; Middle Aged; Biomarkers; Cartilage, Articular; Arthroplasty, Replacement, Knee
PubMed: 38802533
DOI: 10.1038/s41598-024-62614-x -
Frontiers in Immunology 2024Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent synovial inflammation and progressive joint destruction. Macrophages are key... (Review)
Review
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent synovial inflammation and progressive joint destruction. Macrophages are key effector cells that play a central role in RA pathogenesis through their ability to polarize into distinct functional phenotypes. An imbalance favoring pro-inflammatory M1 macrophages over anti-inflammatory M2 macrophages disrupts immune homeostasis and exacerbates joint inflammation. Multiple signaling pathways, including Notch, JAK/STAT, NF-κb, and MAPK, regulate macrophage polarization towards the M1 phenotype in RA. Metabolic reprogramming also contributes to this process, with M1 macrophages prioritizing glycolysis while M2 macrophages utilize oxidative phosphorylation. Redressing this imbalance by modulating macrophage polarization and metabolic state represents a promising therapeutic strategy. Furthermore, complex bidirectional interactions exist between synovial macrophages and fibroblast-like synoviocytes (FLS), forming a self-perpetuating inflammatory loop. Macrophage-derived factors promote aggressive phenotypes in FLS, while FLS-secreted mediators contribute to aberrant macrophage activation. Elucidating the signaling networks governing macrophage polarization, metabolic adaptations, and crosstalk with FLS is crucial to developing targeted therapies that can restore immune homeostasis and mitigate joint pathology in RA.
Topics: Humans; Arthritis, Rheumatoid; Macrophages; Signal Transduction; Synovial Membrane; Fibroblasts; Animals; Macrophage Activation; Cell Communication; Metabolic Reprogramming
PubMed: 38799455
DOI: 10.3389/fimmu.2024.1394108 -
Frontiers in Immunology 2024levels are elevated in the blood and synovial fluid of patients with inflammatory arthritis. can be produced by Th17 cells and locally within joints by tissue-resident...
OBJECTIVES
levels are elevated in the blood and synovial fluid of patients with inflammatory arthritis. can be produced by Th17 cells and locally within joints by tissue-resident cells. induces osteoblast mineralization . As osteoproliferation and Th17 cells are important factors in the pathogenesis of axial spondyloarthritis (axSpA), we aimed to clarify the cellular sources of in spondyloarthritis.
METHODS
Serum, peripheral blood mononuclear cells ( = 15-35) and synovial tissue ( = 3-9) of adult patients with axSpA, psoriatic arthritis (PsA) and rheumatoid arthritis (RA) and healthy controls (HCs, = 5) were evaluated by ELISA, flow cytometry including PrimeFlow assay, immunohistochemistry and immunofluorescence and quantitative PCR.
RESULTS
Synovial tissue of axSpA patients shows significantly more -positive cells than that of HCs ( < 0.01), but numbers are also elevated in PsA and RA patients. Immunofluorescence shows co-localization of with CD68, but not with CD3, SMA, CD163, cadherin-11, or CD90. is elevated in the serum of RA and PsA (but not axSpA) patients compared with HCs ( < 0.001 and < 0.01). However, peripheral blood CD4 T cells from axSpA and PsA patients show higher positivity for in the PrimeFlow assay compared with HCs. CD4 memory T cells from axSpA patients produce more under Th17-favoring conditions (IL-1β and IL-23) than cells from PsA and RA patients or HCs.
CONCLUSION
production is increased in the synovial tissue of SpA and can be localized to CD68 macrophage-like synoviocytes, whereas circulating Th17 cells are only modestly enriched. Considering the osteoproliferative properties of , this offers new therapeutic options independent of Th17 pathways.
Topics: Humans; Arthritis, Psoriatic; Synoviocytes; Male; Adult; Female; Antigens, CD; Interleukins; Middle Aged; Antigens, Differentiation, Myelomonocytic; Axial Spondyloarthritis; Th17 Cells; Synovial Membrane; Joints; Arthritis, Rheumatoid
PubMed: 38799447
DOI: 10.3389/fimmu.2024.1355824 -
Frontiers in Pharmacology 2024Myocardial infarction (MI), the most prevalent ischemic heart disease, constitutes a primary cause of global cardiovascular disease with incidence and mortality. The...
Myocardial infarction (MI), the most prevalent ischemic heart disease, constitutes a primary cause of global cardiovascular disease with incidence and mortality. The pathogenesis of MI is exceedingly intricate, with PANoptosis playing a pivotal role in its pathological process. Xian Ling Gu Bao capsule (XLGB) contains various active components, including flavonoids, terpenes, and phenylpropanoids, and exhibits a wide range of pharmacological activities. However, it remains unclear whether XLGB can protect the myocardium from damage after MI. This study aimed to investigate the impact of XLGB on isoprenaline (ISO)-induced MI in mice and its potential mechanisms. This study assessed the protective effects of XLGB against ISO-induced MI through techniques such as echocardiography, HE staining, Masson staining, and enzyme-linked immunosorbent assay (ELISA). Furthermore, the potential mechanisms of XLGB's protective effects on MI were explored using bioinformatics, molecular docking, and molecular dynamics simulations. These mechanisms were further validated through immunofluorescence staining and Western blotting. The results demonstrated that various doses of XLGB exhibited a significant reduction in myocardial injury induced by myocardial infarction. Intriguingly, higher dosages of XLGB displayed superior therapeutic efficacy compared to the positive control metoprolol. This protective effect is primarily achieved through the inhibition of oxidative stress and the inflammatory processes. Furthermore, we have elucidated that XLGB protected the myocardium from MI-induced damage by suppressing PANoptosis, with a critical role played by the NLRP3/Caspase3/RIP1 signaling pathway. Of particular note, the primary compounds of XLGB were found to directly interact with NLRP3/Caspase3/RIP1, a discovery further validated through molecular docking and molecular dynamics simulations. This suggests that NLRP3/Caspase3/RIP1 may be a therapeutic target for XLGB-induced myocardial protection. In summary, our findings reveal a novel property of XLGB: reverses myocardial damage following MI by inhibiting the NLRP3/Caspase3/RIP1-mediated PANoptosis pathway.
PubMed: 38799163
DOI: 10.3389/fphar.2024.1391511 -
Medicina (Kaunas, Lithuania) Apr 2024(1) : Despite documented clinical and pain discrepancies between male and female osteoarthritis (OA) patients, the underlying mechanisms remain unclear. Synovial...
(1) : Despite documented clinical and pain discrepancies between male and female osteoarthritis (OA) patients, the underlying mechanisms remain unclear. Synovial myofibroblasts, implicated in synovial fibrosis and OA-related pain, offer a potential explanation for these sex differences. Additionally, interleukin-24 (IL24), known for its role in autoimmune disorders and potential myofibroblast production, adds complexity to understanding sex-specific variations in OA. We investigate its role in OA and its contribution to observed sex differences. (2) : To assess gender-specific variations, we analyzed myofibroblast marker expression and levels in synovial tissue samples from propensity-matched male and female OA patients (each = 34). Gene expression was quantified using quantitative polymerase chain reaction (qPCR). The association between expression levels and pain severity, measured by a visual analog scale (VAS), was examined to understand the link between and OA pain. Synovial fibroblast subsets, including CD45-CD31-CD39- (fibroblast) and CD45-CD31-CD39+ (myofibroblast), were magnetically isolated from female patients ( = 5), and expression was compared between these subsets. (3) : Females exhibited significantly higher expression of myofibroblast markers (MYH11, ET1, ENTPD2) and compared to males. expression positively correlated with pain severity in females, while no correlation was observed in males. Further exploration revealed that the myofibroblast fraction highly expressed compared to the fibroblast fraction in both male and female samples. There was no difference in the myofibroblast fraction between males and females. (4) : Our study highlights the gender-specific role of myofibroblasts and IL24 in OA pathogenesis. Elevated IL24 levels in females, correlating with pain severity, suggest its involvement in OA pain experiences. The potential therapeutic implications of IL24, demonstrated in autoimmune disorders, open avenues for targeted interventions. Notwithstanding the limitations of the study, our findings contribute to understanding OA's multifaceted nature and advocate for future research exploring mechanistic underpinnings and clinical applications of IL24 in synovial myofibroblasts. Additionally, future research directions should focus on elucidating the precise mechanisms by which IL24 contributes to OA pathology and exploring its potential as a therapeutic target for personalized medicine approaches.
Topics: Humans; Female; Male; Myofibroblasts; Interleukins; Synovial Membrane; Osteoarthritis; Middle Aged; Aged; Propensity Score; Sex Factors; Pain
PubMed: 38792924
DOI: 10.3390/medicina60050741 -
Medicina (Kaunas, Lithuania) Apr 2024: The number of hip arthroscopy procedures is on the rise worldwide, and awareness regarding proper management of the hip capsule has increased. No capsulotomy shape is...
: The number of hip arthroscopy procedures is on the rise worldwide, and awareness regarding proper management of the hip capsule has increased. No capsulotomy shape is agreed upon as a standard approach, with literature supporting both isolated interportal and T-shaped capsulotomies. The aim of this retrospective cohort study is to report the clinical results of a standardized extended interportal capsulotomy (EIPC) during hip arthroscopy. : Patients operated on between 2017 and 2020 with a hip arthroscopy were eligible. The inclusion criteria were ages 18-60 years, failed non-operative treatment, and at least a 2-year follow-up. Exclusion criteria were bilateral femoroacetabular impingement syndrome (FAS) cases or labral lesions, ipsilateral knee injury, history of ipsilateral hip surgery, and significant spine lesions. Data regarding demographic characteristics such as age, gender, operation date, BMI, but also Beighton score, presence of postoperative pudendal nerve damage, and revision for any reason were gathered from patients' records. All patients were evaluated preoperatively with a visual analog scale (VAS), the Hip Disability and Osteoarthritis Outcome Score (HOOS), and the modified Harris Hip Score (mHHS). : Of the 97 patients operated on with a hip arthroscopy between the defined dates, only 90 patients were included. The mean age was 37.9 ± 9.8, and 58.9% of patients were male. The most frequent surgical indication was an isolated FAS lesion (73.3%), followed by FAS associated with a labral tear (12.2%), an isolated labrum tear (10.0%), synovitis (3.3%), and a loose body (1.1%). The mean follow-up for the study cohort was 39.3 months. The majority of the patients had uneventful surgeries (76.7%), while there were three cases of sciatic nerve neuropraxia and 12 cases of pudendal nerve neuropraxia. Two patients underwent revision surgery during the study period. Comparison between preoperative and postoperative clinical scores showed a significant improvement with a final mHHS mean value of 67.7 ± 18.2, an HOOS value of 74.1 ± 13.2, and a low VAS score of 1.3 ± 1.2. : A hip arthroscopy procedure with a standardized and unrepaired, extended interportal capsulotomy is a safe procedure with satisfactory mid-term results and high overall patient satisfaction. At a minimum of 2 years and a mean of 39.2 months, patients showed improved clinical scores and a low revision rate.
Topics: Humans; Adult; Male; Female; Retrospective Studies; Middle Aged; Arthroscopy; Hip Joint; Adolescent; Joint Capsule; Treatment Outcome; Cohort Studies; Young Adult; Femoracetabular Impingement
PubMed: 38792921
DOI: 10.3390/medicina60050738 -
Medicina (Kaunas, Lithuania) Apr 2024: The interspace between the popliteal artery and the posterior capsule of the knee (iPACK) block has been widely used in perioperative settings to control posterior...
Investigation of Optimal Needle Position for Radiofrequency Ablation-Based Blockade of Interspace between the Popliteal Artery and the Posterior Capsule of the Knee: A Cadaveric Study.
: The interspace between the popliteal artery and the posterior capsule of the knee (iPACK) block has been widely used in perioperative settings to control posterior knee pain and can additionally be used for chronic knee pain. In this cadaveric study, we aimed to investigate the needle tip position and its proximity to the articular branch of the tibial nerve (ABTN) during an iPACK-targeted radiofrequency procedure. : An ultrasound-guided iPACK block was performed on 20 knees of 10 cadavers. We injected 0.1 mL each of blue and green gelatinous dye near the tibial artery (point A) and posterior knee capsule (point B), respectively, and evaluated the spread of both around the ABTN. For a hypothetical conventional radiofrequency ablation (RFA) lesion (diameter, 2.95 mm) and cooled RFA lesion (diameter, 4.9 mm), we counted the number of specimens in which the ABTNs would be captured. : The percentage of specimens in which the ABTN would be captured by a cooled RFA lesion was 64.71% at point A and 43.75% at point B ( = 0.334). Meanwhile, the percentage of specimens in which the ABTN would be captured by a conventional RFA lesion was 58.82% from point A and 25% from point B ( = 0.065). : When performing an RFA-based iPACK block, the needle tip may be positioned either lateral to the tibial artery or in the space between the posterior knee capsule and the tibial artery. However, more studies with larger samples are needed to verify these results before the clinical use of this procedure can be recommended.
Topics: Humans; Cadaver; Popliteal Artery; Radiofrequency Ablation; Female; Male; Nerve Block; Needles; Aged; Knee Joint; Aged, 80 and over; Tibial Nerve; Ultrasonography, Interventional
PubMed: 38792872
DOI: 10.3390/medicina60050689