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Indian Journal of Orthopaedics Jun 2024Rubber band constriction syndrome has been described in the literature, although there are very few case reports. Non-healing recurrent tenosynovitis and synovitis of...
Rubber band constriction syndrome has been described in the literature, although there are very few case reports. Non-healing recurrent tenosynovitis and synovitis of the wrist joint demonstrating a circular rubber band on imaging has not been described before. Imaging studies showed retained circular band deep to the extensor tendons, embedded within the joint capsule. Surgical removal of the band by open incision led to a dramatic improvement in the outcome of the patient. V.
PubMed: 38812874
DOI: 10.1007/s43465-024-01151-1 -
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 -
Journal of Shoulder and Elbow Surgery May 2024The pathophysiology of frozen shoulder (FS) involves abnormal expressions of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) that...
BACKGROUND
The pathophysiology of frozen shoulder (FS) involves abnormal expressions of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) that lead capsular fibrosis. However, there has been little concern for why diabetic FS has more protracted fibrotic condition. The objective of this study was to compare the expression levels of MMPs and TIMPs in the joint capsule of patients with diabetic and non-diabetic FS.
MATERIALS AND METHODS
Samples of capsular tissue were collected from 20 patients with FS (10 diabetic patients; diabetic group, and 10 non-diabetic patients; non-diabetic group) and 10 patients (control group) with chronic anterior shoulder instability. Quantitative real-time RT-PCR and Western blot analysis were performed to determine the expression levels of mRNA and protein for MMP-1, 3, 9, 13, 14, and TIMP-1, 2.
RESULTS
The results of quantitative real-time RT-PCR showed significantly higher expression levels of all MMPs and TIMP-1 and significantly lower expression levels of TIMP-2 in the joint capsule of patients in the diabetic or non-diabetic groups compared with the control group. Significantly higher expression levels of MMP-1, 9, 14, and TIMP-1 were detected in the diabetic group compared with the non-diabetic group. The results of Western blot analysis showed significantly higher levels of MMP-3, 13, 14, and TIMP-1 in the joint capsule of patients in the diabetic or non-diabetic groups compared with the control group. However, no significant differences of protein levels of them were observed between diabetic and non-diabetic groups.
CONCLUSIONS
The findings of this study demonstrate the potential involvement of MMP-1 and 9 in the pathophysiology of diabetic FS. These findings may be helpful in identification of therapeutic targets for development of novel treatments for this protracted chronic fibrosing condition.
PubMed: 38810916
DOI: 10.1016/j.jse.2024.03.062 -
International Immunopharmacology Jul 2024Defective clearance of apoptotic cells due to impaired efferocytosis sustains error in self-tolerance that exacerbates rheumatoid arthritis (RA). However, the molecular...
IL-17A/IL-17RA interaction blockade sensitizes synovial macrophages to efferocytosis and PD-L1 signaling via rewiring STAT-3/ADAM17/MERTK axis in rheumatoid arthritis animal model.
Defective clearance of apoptotic cells due to impaired efferocytosis sustains error in self-tolerance that exacerbates rheumatoid arthritis (RA). However, the molecular determinant that directly or specifically impairs efferocytosis in RA is not yet studied. We identified a new perspective that IL-17A significantly impedes efferocytosis via preferential activation of the JAK/STAT-3/ADAM17 signaling axis. In contrast, disruption of the IL-17A/IL-17RA interaction using cyanidin or silencing of IL-17RA obstructed JAK/STAT-3 activation that further abolished ADAM17 expression. Subsequent depletion of ADAM17 inhibited the shedding of Mer tyrosine kinase receptor (MERTK), which significantly increased apoptotic cell intake and restored efferocytosis in adjuvant-induced arthritic (AA) model. Concomitantly, the amplification of the efferocytosis process due to IL-17A/IL-17RA interaction disruption was sensitive to mitochondrial fission mediated via Drp-1 phosphorylation downstream of STAT-3 inhibition. As expected, cyanidin treated AA synovial macrophages that exhibited increased efferocytosis demonstrated a phenotypic shift towards CD163 anti-inflammatory phenotype in a STAT-5 dependent manner. Similar results were obtained in IL-17A-sensitized AA synovial macrophages treated with S3I-201 (a STAT-3 inhibitor) indicating that IL-17A influences efferocytosis via the STAT-3 pathway. In view of our previous work where cyanidin restored Th17/Treg balance, our present investigation fulfils a critical gap by providing scientific validation that cyanidin escalated PD-L1 expression during the efferocytosis process that could have impacted the restoration of Th17/Treg balance in an AA model. Together, these data corroborate the hypothesis that IL-17A signaling can impair efferocytosis via regulating STAT-3/ADAM17/FL-MERTK axis and that its inhibition can amplify a pro-resolution signal against RA progression.
Topics: Interleukin-17; Animals; STAT3 Transcription Factor; Arthritis, Rheumatoid; Macrophages; Signal Transduction; B7-H1 Antigen; Mice; Receptors, Interleukin-17; Anthocyanins; Arthritis, Experimental; Humans; Disease Models, Animal; Phagocytosis; Male; Synovial Membrane; Mice, Inbred C57BL; Apoptosis; Efferocytosis
PubMed: 38810305
DOI: 10.1016/j.intimp.2024.112343 -
Current Rheumatology Reviews 2024Synovial hemangioma is a benign soft-tissue tumor of vascular origin. Hemangioma only accounts for 1% of all bone lesions and is mostly an incidental finding among the...
INTRODUCTION
Synovial hemangioma is a benign soft-tissue tumor of vascular origin. Hemangioma only accounts for 1% of all bone lesions and is mostly an incidental finding among the primary skeleton tumors. A delay in diagnosis results in joint degeneration and osteoarthritic damage because of infiltrating tumor growth.
CASE PRESENTATION
We presented a rare case of an intra-articular synovial hemangioma in a 13- year-old pediatric patient who was asymptomatic for 5 years. She attended orthopedics OPD at AIIMS, Mangalagiri. Surgical excision of the mass and partial synovectomy was done. Synovial hemangioma came out to be the diagnosis following a histologic study.
CONCLUSION
As radiography has limited diagnostic ability, synovial hemangiomas are difficult and challenging to identify on an outpatient basis. Histological examination and magnetic resonance imaging are extremely helpful. To minimize the hemarthrosis risks, early complete excision can be used as the best treatment modality.
Topics: Humans; Female; Adolescent; Hemangioma; Knee Joint; Synovial Membrane; Arthralgia; Synovectomy; Soft Tissue Neoplasms; Magnetic Resonance Imaging; Edema
PubMed: 38807471
DOI: 10.2174/0115733971266035231123154807 -
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