It's not always histiocytic sarcoma: Immunocytochemistry to identify two unusual tumors in a Bernese Mountain dog.

A 7-year-old female spayed Bernese Mountain dog was presented for evaluation of hematuria. Incidentally, a right stifle sarcoma was diagnosed via cytology, which raised concern for histiocytic sarcoma (given the patient's signalment) versus another joint-associated sarcoma. Histopathology and immunohistochemistry revealed a CD18-negative, non-histiocytic origin cell population. Findings were consistent with a joint-associated grade II soft tissue sarcoma (STS). The patient's hematuria was progressive over 5 months, and urinary bladder transitional cell carcinoma (TCC) was diagnosed via cystoscopy and histopathology. An enlarged right medial iliac lymph node was identified on routine restaging via abdominal ultrasound 3 months later. Cytology of the lymph node revealed a markedly pleomorphic cell population, again raising concern for histiocytic sarcoma (HS). Other differentials included an anaplastic metastatic population from the joint-associated STS or the TCC. Immunocytochemistry revealed a cytokeratin-positive, CD18-, CD204-, and vimentin-negative cell population, consistent with a carcinoma. DNA was extracted from cytology slides to sequence cells for BRAF mutation status. Sequencing revealed a homozygous V596E (transcript ENSCAFT00845055173.1) BRAF mutation, consistent with the known biology of TCC. In neither case was HS truly present in this patient, but immunocytochemistry provided information that helped to optimize the patient's chemotherapy recommendations.

Metabolite-sensing GPCRs in rheumatoid arthritis.

Persistent inflammation in damaged joints results in metabolic dysregulation of the synovial microenvironment, causing pathogenic alteration of cell activity in rheumatoid arthritis (RA). Recently, the role of metabolite and metabolite-sensing G protein-coupled receptors (GPCRs) in the RA-related inflammatory immune response (IIR) has become a focus of research attention. These GPCRs participate in the progression of RA by modulating immune cell activation, migration, and inflammatory responses. Here, we discuss recent evidence implicating metabolic dysregulation in RA pathogenesis, focusing on the connection between RA-related IIR and GPCR signals originating from the synovial joint and gut. Furthermore, we discuss future directions for targeting metabolite-sensing GPCRs for therapeutic benefit, emphasizing the importance of identifying endogenous ligands and investigating the various transduction mechanisms involved.

Mangiferin inhibits proliferation,migration and inflammatory factor expression of fibroblast-like synoviocytes in rheumatoid arthritis / 中国组织工程研究

BACKGROUND:Mangiferin is a biphenylpyridone compound extracted from mango leaves,bark and roots.Previous studies have shown that mangiferin can exert anti-systemic inflammatory effects through the activation of transcription factors such as NF-κB and JAK/STAT. OBJECTIVE:To investigate the effects and mechanisms of mangiferin on proliferation,migration and inflammatory factor release of rheumatoid arthritis fibroblast-like synovial cells(RA-FLS). METHODS:RA-FLS were divided into blank group,R848(TLR7/8 agonists)stimulated group,mangiferin low-,medium-,high-dose groups(2,4 and 8 μg/mL)and positive control group(Cu-CPT8,TLR8 pathway inhibitor).The cytotoxic effect of different mass concentrations of mangiferin was detected using cell counting kit-8 method and the final cellular dosing mass concentration was screened.The proliferation ability of RA-FLS was detected by cell clone formation assay,the migration ability of RA-FLS was detected by scratch assay and Transwell migration assay,and the expression of interleukin 1β,interleukin 6 and tumor necrosis factor α mRNA in RA-FLS was detected by qRT-PCR. RESULTS AND CONCLUSION:Compared with the blank group,the viability of RA-FLS was inhibited after treatment with mangiferin at 2-10 μg/mL,but there was no significant difference among groups(P>0.05),indicating that the toxic effect on RA-FLS was minimal.Compared with the R848-stimulated group,mangiferin decreased the number of cell clones,the scratch healing rate and the number of migrating cells in all dosing groups(P<0.01);and the expression of interleukin 1β,interleukin 6 and tumor necrosis factor α mRNA was also reduced in the mangostin medium-and high-dose groups(P<0.01).Compared with the R848-stimulated group,the number of cell clones,the scratch healing rate and the number of migrating cells as well as the expression levels of interleukin 6 and tumor necrosis factor α mRNA were significantly reduced in the positive control group(P<0.05,P<0.01).But there was no significant difference in the expression level of interleukin 1β.To conclude,mangiferin may exert its anti-rheumatoid arthritis effects through the TLR7/8 signaling pathway by inhibiting RA-FLS proliferation,migration,and inflammatory factor release.

[Corrigendum] Role of cysteine­rich angiogenic inducer 61 in fibroblast­like synovial cell proliferation and invasion in rheumatoid arthritis.

Following the publication of the above article, an interested reader drew to the authors' attention that Fig. 4A on p. 921, showing the results from cell migration assay experiments, featured a pair of duplicated data panels. After having consulted their original data, the authors have realized that Fig. 3A on the same page, showing the fluorometric images of apoptotic cells, also contained a pair of duplicated data panels. These errors in the presentation of these figures arose inadvertently as a consequence of selecting the wrong images for the 'RA NC' data panel in Fig. 3A and the NOR-FLS data panel in Fig. 5E. The revised versions of Figs. 3 and 4 are shown on the next two pages. All the authors approve of the publication of this corrigendum, and the authors are grateful to the Editor of Molecular Medicine Reports for granting them the opportunity to publish this. The authors regret their oversight in allowing these errors to be included in the paper, and also apologize to the readership for any inconvenience caused. [Molecular Medicine Reports 11: 917­923, 2015; DOI: 10.3892/mmr.2014.2770].

Baicalin inhibits PDK1 to mediate glucose metabolism reprogramming and intervene rheumatoid arthritis synovial inflammation / 药学学报

This study started from the effect of baicalin (BC), the main active component of the labiaceae plant Scutellaria baicalensis, on collagen-induced arthritis (CIA) in rats, to explore the mechanism of glucose metabolism reprogramming in fibroblast like synoviocytes (FLSs), a key effector cell of synovial inflammation in rheumatoid arthritis (RA). First of all, CIA rats and tumor necrosis factor-α (TNF-α)-induced RASFs in vitro and in vivo models were established, the arthritis index (AI) score and histopathological changes of CIA rats after BC administration were observed, and the levels of inflammatory factors in serum and cell supernatant were quantified by ELISA, immunocytochemistry and Western blot were used to detect the expression of G-protein-coupled receptor 81 (GPR81) and pyruvate dehydrogenase kinase 1 (PDK1) proteins. In addition, the kit was used to measure the levels of key products and enzyme activities in glucose metabolism reprogramming. The results showed that BC (50, 100 and 200 mg·kg-1) could alleviate the symptoms of arthritis in CIA rats in a dose-dependent manner, inhibit synovial hyperplasia, alleviate the infiltration of inflammatory cells, down-regulate the levels of pro-inflammatory factors TNF-α and interleukin (IL)-1β, and up-regulate the levels of anti-inflammatory factor IL-10 in CIA rats. At the same time, the secretion levels of lactate, pyruvate, acetyl-CoA, citrate and the activity of lactate dehydrogenase B (LDH-B) were decreased, and the expressions of GRP81 and PDK1 were down-regulated, suggesting that BC mediated the reprogramming process of glucose metabolism. However, when GPR81 inhibitor 3-OBA inhibited lactate uptake, the activity of LDH-B was significantly increased, suggesting that BC inhibited the expression of PDK1, a key enzyme in the reprogramming metabolism from glycolysis to oxidative phosphorylation. All animal experiments in this study were conducted in accordance with the ethical standards of the Laboratory Animal Care Center of Anhui University of Chinese Medicine (approval number: AHUCM-rats-2021049). These studies revealed that baicalin mediated metabolic reprogramming of RASFs from glycolysis to oxidative phosphorylation by inhibiting PDK1 protein expression, and alleviated joint inflammation in CIA rats.

A Primary Mediastinal Monophasic Spindle-Cell Synovial Sarcoma with Superior Venacaval Obstruction.

Primary mediastinal sarcoma is a rare tumour that usually presents with nonspecific symptoms such as hoarseness, dyspnoea, and chest pain. Superior vena cava (SVC) syndrome is an extremely uncommon complication that is caused by the compression, invasion, and thrombosis of the SVC or brachiocephalic veins. SVC syndrome can present as asymptomatic cases or as rare life-threatening emergencies with upper airway obstruction and increased intracranial pressure. This report describes the case of a 58-year-old female who presented with swelling of the face, neck, and upper limbs associated with dyspnoea on exertion. The radiological investigations revealed a large well-defined central necrotic peripherally enhancing lesion in the superior mediastinum extending anteriorly with the compression of brachiocephalic veins. A histopathological examination detected spindle cells arranged in fascicles with nuclear atypia with immunohistochemistry positive for creatine kinase (CK), smooth muscle actin (SMA), desmin and CD99. These findings established the diagnosis of a mediastinal monophasic synovial sarcoma with SVC obstruction. The patient was initiated on palliative radiotherapy for the management of the SVC, followed by systemic biological treatment with the tyrosine kinase inhibitor pazopanib, and was clinically improved. It is essential to promptly diagnose and treat this condition, especially when SVC syndrome manifests.

Disease Markers and Therapeutic Targets for Rheumatoid Arthritis Identified by Integrating Bioinformatics Analysis with Virtual Screening of Traditional Chinese Medicine.

OBJECTIVE: The aim of this study was to identify potentially important Rheumatoid arthritis (RA) targets related to immune cells based on bioinformatics analysis, and to identify small molecules of traditional Chinese medicine (TCM) associated with these targets that have potential therapeutic effects on RA. METHODS: Gene expression profile data related to RA were downloaded from the Gene Expression Omnibus (GSE55235, GSE55457, and GSE77298), and datasets were merged by the batch effect removal method. The RA key gene set was identified by protein-protein interaction network analysis and machine learning-based feature extraction. Furthermore, immune cell infiltration analysis was carried out on all DEGs to obtain key RA markers related to immune cells. Batch molecular docking of key RA markers was performed on our previously compiled dataset of small molecules in TCM using AutoDock Vina. Moreover, in vitro experiments were performed to examine the inhibitory effect of screened compounds on the synovial cells of an RA rat model. RESULTS: The PPI network and feature extraction with machine learning classifiers identified eight common key RA genes: MYH11, CFP, LY96, IGJ, LPL, CD48, RAC2, and CSK. RAC2 was significantly correlated with the infiltration and expression of five immune cells, with significant differences in these immune cells in the normal and RA samples. Molecular docking and in vitro experiments also showed that sanguinarine, sesamin, and honokiol could effectively inhibit the proliferation of RA rat synovial cells, also could all effectively inhibit the secretion of TNF-α and IL-1ß in synovial cells, and had a certain inhibitory effect on expression of the target protein RAC2. CONCLUSIONS: The core gene set of RA was screened from a new perspective, revealing biomarkers related to immune cell infiltration. Using molecular docking, we screened out TCM small molecules for the treatment of RA, providing methods and technical support for the treatment of RA with TCM.

Krill Oil Attenuates Inflammation in Monosodium Iodoacetate-Induced Osteoarthritic Rats, SW982 Synovial Cell Line, and Primary Chondrocytes.

The aim of this study was to investigate the effects of krill oil (FJH-KO) in monoiodoacetate (MIA)-induced osteoarthritis in rat models, and H2O2- or lipopolysaccharide (LPS)-treated primary chondrocytes and the SW982 synovial cell line. We found that 150 mg/kg b.w. FJH-KO supplementation increased running speed, stride, and foot pressure in MIA-induced osteoarthritic rats. In the H2O2-treated SW982 synovial cell line and primary chondrocytes, FJH-KO treatment prevented cell death and suppressed matrix degradation by increasing the levels of anabolic factors of cartilage tissue, including aggrecan, collagen type Ⅰ, collagen type Ⅱ, tissue inhibitors of metalloproteinase (TIMP)-1, and TIMP-3, and decreasing those of catabolic factors of cartilage tissue, including phosphorylation of Smad, MMP-3, and MMP-13. In addition, FJH-KO treatment suppressed the activation of inflammation and apoptosis pathways in the LPS-treated SW982 synovial cell line and primary chondrocytes. We suggest that FJH-KO supplementation may help prevent osteoarthritis progression because of its direct effects on inflammation and apoptosis of chondrocytes.

Kruppel like factor 10 up-regulates PDZ and LIM domain containing protein 2 via nuclear factor kappa-B pathway to inhibit proliferation and inflammatory of fibroblastoid synovial cell in rheumatoid arthritis.

Rheumatoid arthritis (RA) is an autoimmune disease caused by synovitis. Two genes, KLF10 (Kruppel like factor 10) and PDZ and LIM domain containing protein 2 (PDLIM2), play key roles in cell inflammation and proliferation. However, the specific roles of the two on inflammation and proliferation of RA-fibroblastoid synovial cell (RA-FLS) have not been reported so far. RT-qPCR and Western blot detected the expressions of PDLIM2 and KLF10 in Human Rheumatoid arthritis FLSs (HFLSs-RA). Cell transfection techniques overexpressed PDLIM2 and KLF10 or inhibited the expression of KLF10. JAPAR database predicted the binding sites of PDLIM2 and KLF10, and the binding between the two was detected and verified using luciferase reporter genes and ChIP. Subsequently, CCK-8 technology, TUNEL staining, Western blot, wound healing and ELISA detected proliferation-related indicators, migration-related indications and inflammation-related indicators. Finally, western blot was used to detect the expression of NF-κB pathway-related proteins to further explore the mechanism.The expression of PDLIM2 was decreased in HFLSs-RA. Overexpression of PDLIM2 inhibited proliferation, migration and inflammation in HFLSs-RA. KLF10 can transcriptionally activate PDLIM2. Interfering with KLF10 reversed the inhibition effects of PDLIM2 overexpression on the proliferation, migration and inflammation, which was possibly through the NF-κB pathway. Overall, KLF10 can up-regulate PDLIM2 by regulating the NF-κB pathway to inhibit inflammation and proliferation of HFLSs-RA.

[Implementation of a standardized clinical test kit for diagnostics of periprosthetic infections in the clinical routine. German version]. / Implementierung eines standardisierten Test-Kits zur Diagnostik von periprothetischen Infektionen in der klinischen Routine.

BACKGROUND: The number of primary arthroplasties is increasing and the proportion of revision arthroplasties is becoming increasingly more important. The need for standardized and guideline-based diagnostics for the safe detection of a periprosthetic joint infection (PJI) is becoming apparent. In the past 10 years various organizations have published definitions and diagnostic guidelines. The implementation of an inhouse standard test kit could help to simplify the process and could improve the diagnostic quality. METHOD: In 2016 a test kit was compiled in a monocentric prospective study, taking the International Consensus Meeting (ICM) criteria 2014 and the Infectious Diseases Society of America (IDSA) criteria into account, which also fulfils the definitions of the ICM criteria 2018 and criteria of the European Bone and Joint Infection Society 2021. The test kit was implemented in the clinical setting of a special department for aseptic and septic revision arthroplasty. The usability and accuracy of the test kit were examined. RESULTS: The test kit was implemented using blood samples (leukocyte count; C­reactive protein, CRP), samples for examining the synovial fluid (white blood cell count, PMN cell differentiation, microbiological culture for incubation over 14 days, alpha-defensin enzyme-linked immunosorbent assay, ELISA, leukocyte esterase test strips) together with information and request forms. Between April 2016 and February 2020 a total of 405 patients were investigated. Within 3 calendar years, the use of the test kit increased from 59% initially to 86%, and finally to 96% of cases in the third calendar year. The leukocyte esterase test strip was reliable in only 72%, due to undifferentiated readability or blood contamination. The costs increased by the only commercially available alpha-defensin ELISA test by approx. 52€ per puncture. The best individual test showed a sensitivity/specificity of 92.8%/95.2% with alpha-defensin. It was calculated which combinations showed a similar test quality and different combinations, such as CRP+ cell count+ microbiology showed a sensitivity/specificity both of around 90%. Metallosis is a challenge for preoperative PJI diagnostics. DISCUSSION: In a prospective study it was shown, that the implementation of the standardized test kit lead to a guideline based PJI diagnostic in all cases and thus to a significantly increase of the diagnostic quality. There is currently no single test that reliably excludes or proves an infection. The alpha-defensin laboratory ELISA test showed the best test accuracy, whereby the consideration of test combinations is obligatory and at the same time safe.

Implementation of a standardized clinical test kit for diagnostics of periprosthetic infections in the clinical routine.

BACKGROUND: The number of primary arthroplasties is increasing and the proportion of revision arthroplasties is becoming increasingly more important. The need for standardized and guideline-based diagnostics for the safe detection of a periprosthetic joint infection (PJI) is becoming apparent. In the past 10 years various organizations have published definitions and diagnostic guidelines. The implementation of an inhouse standard test kit could help to simplify the process and could improve the diagnostic quality. METHOD: In 2016 a test kit was compiled in a monocentric prospective study, taking the International Consensus Meeting (ICM) criteria 2014 and the Infectious Diseases Society of America (IDSA) criteria into account, which also fulfils the definitions of the ICM criteria 2018 and criteria of the European Bone and Joint Infection Society 2021. The test kit was implemented in the clinical setting of a special department for aseptic and septic revision arthroplasty. The usability and accuracy of the test kit were examined. RESULTS: The test kit was implemented using blood samples (leukocyte count; C­reactive protein, CRP), samples for examining the synovial fluid (white blood cell count, PMN cell differentiation, microbiological culture for incubation over 14 days, alpha-defensin enzyme-linked immunosorbent assay, ELISA, leukocyte esterase test strips) together with information and request forms. Between April 2016 and February 2020 a total of 405 patients were investigated. Within 3 calendar years, the use of the test kit increased from 59% initially to 86%, and finally to 96% of cases in the third calendar year. The leukocyte esterase test strip was reliable in only 72%, due to undifferentiated readability or blood contamination. The costs increased by the only commercially available alpha-defensin ELISA test by approx. 52€ per puncture. The best individual test showed a sensitivity/specificity of 92.8%/95.2% with alpha-defensin. It was calculated which combinations showed a similar test quality and different combinations, such as CRP+ cell count+ microbiology showed a sensitivity/specificity both of around 90%. Metallosis is a challenge for preoperative PJI diagnostics. DISCUSSION: In a prospective study it was shown, that the implementation of the standardized test kit lead to a guideline based PJI diagnostic in all cases and thus to a significantly increase of the diagnostic quality. There is currently no single test that reliably excludes or proves an infection. The alpha-defensin laboratory ELISA test showed the best test accuracy, whereby the consideration of test combinations is obligatory and at the same time safe.

Primary synovial sarcoma of thyroid gland: A case report and review of literature.

INTRODUCTION AND IMPORTANCE: Synovial cell sarcoma (SS) is an extremely rare mesenchymal malignancy, representing nearly 10% of all soft-tissue sarcomas. These high-grade soft tissue sarcomas commonly arise in the para-articular regions of lower extremities. However, 15% of Synovial sarcomas has been described at Unusual locations, including head, neck, and trunk. Herein, we describe the twelfth case of primary synovial cell sarcoma of thyroid with a literature review. CASE PRESENTATION: A 43-year-old woman presented with complaint of a progressive neck mass for the last five-months. She developed with dysphagia and dyspnea nearly 2 months prior, without signs of hoarseness, and weight loss. Ultrasonography in which revealed a heterogeneous, hypervascularized thyroid mass. After total thyroidectomy immunohistochemistry was in favor of primary synovial cell sarcoma of thyroid. The diagnosis was confirmed via Molecular genetic analysis of the SYT-SSX fusion gene transcript using the RT- polymerase chain reaction method. Clinical Discussion: Primary thyroid SVS is an extremely rare malignancy with poor biological behavior. SVS has been known for its tendency to local and distal re-occurrence after a few years of treatment. SS can be classified into two subtypes of monophasic or biphasic based on the presence of mesenchymal and/or epithelial components. Accordingly, the most accurate diagnostic tool for SS is considered to be molecular genetic analysis for SYT/SSX fusion transcript. CONCLUSION: Herein, we reported an extremely rare case of SVS of thyroid gland. These high-grade soft tissue sarcomas mainly present with an asymptomatic rapid growing neck mass. Unspecific clinical presentations and extreme rarity of this disorder, make the diagnosis of thyroid SVS very challenging. Due to paucity of data, there is not enough evidence to establish a reliable mortality rate. However, the prognosis of thyroid SVS seems unfavorable.

Metabolic changes in synovial cells in early inflammation: Involvement of CREB phosphorylation in the anti-inflammatory effect of 2-deoxyglucose.

The involvement of metabolic reprogramming has been suggested to contribute to the pathophysiology of rheumatoid arthritis (RA). Glycolysis is enhanced in synovial cell metabolism in RA patients. Inhibitors of glycolysis are known to have anti-inflammatory effects. But, changes in the metabolism of normal synovial membranes or synovial cells during the early stages of inflammation remains unknown. Moreover, there are still many aspects of inflammatory signaling pathways altered by glycolysis inhibitors, that remain unclear. In this study we found that, in normal, non-pathological bovine synovial cells, most of ATP synthesis was generated by mitochondrial respiration. However, during the early of stages inflammation, initiated by lipopolysaccharide (LPS) exposure, synovial cells shifted to glycolysis for ATP production. The glycolysis inhibitor 2-deoxyglucose (2DG) reversed LPS induced increases in glycolysis for ATP production and suppressed the expression of inflammatory cytokines and proteolytic enzymes. 2DG suppressed the phosphorylation of the transcription factor cAMP response element binding protein (CREB) enhanced by LPS. Treatment with a CREB inhibitor reversed the expression of LPS-stimulated inflammatory cytokines and proteolytic enzymes. This study showed that changes in metabolism occur during the early stages of inflammation of synovial cells and can be reversed by 2DG and signaling pathways associated with CREB phosphorylation.

Correlation Between Level of Interleukin-37 and Rheumatoid Arthritis Progression.

BACKGROUND: Rheumatoid arthritis (RA) is a systemic autoimmune inflammatory disease that primarily affects joints. Interleukin-37 (IL-37) is an anti-inflammatory cytokine that is known to suppress immune response and inflammation. The objective of this study is to evaluate the correlation between level of IL-37 and RA progression using the disease activity score in 28 joints (DAS-28). METHODS: A total of 87 RA patients were separated into 4 groups based on the DAS28, referred to as the remission, mild, moderate and severe groups. 18 healthy volunteers were also included. Serum level of IL-37 and IL-37 mRNA expression level in peripheral blood mononuclear cells (PBMCs) in each individual participant as well as IL-37 mRNA expression level in synovial cells were assessed to explore their correlation with RA progression. RESULTS: Serum level of IL-37 and IL-37 mRNA expression levels in both PBMCs and synovial cells were all positively correlated with the severity of RA as reflected by the DAS28. Receiver operating characteristic (ROC) analysis revealed area under curve (AUC) values of 1, 0.5262 and 0.7789 for the three parameters. CONCLUSION: Our results suggest that serum IL-37 level and mRNA expression levels of IL-37 in PBMCs and synovial cells are correlated with the severity of RA in a Chinese population.

Design, synthesis and anti-rheumatoid arthritis evaluation of double-ring conjugated enones.

Four series of double-ring conjugated enones were designed, synthesized and studied for the inhibition of synovial cell activity through the modification of Dysodensiol K core structure, double-ring, double-bond and double-carbonyl groups. For in vitro synovial cell assay of rats, compound 151 and 168 exhibited good inhibitory activities, with IC50 values of 2.71 ± 0.18 and 2.68 ± 0.16 µM respectively. At the same time, the LDH release and LD50 test results revealed that the target compounds were low cytotoxicity and acute toxicity. For in vivo CIA model test through the oral administration, compounds 151 and 168 were exhibited similar effect to positive control group methotrexate.

ANGPTL2 Induces Synovial Inflammation via LILRB2.

Angiopoietin-like proteins (ANGPTLs) are circulating proteins that are expressed in various cells and tissues and are thought to be involved in the repair and remodeling of damaged tissues; however, ANGPTL2 hyperfunction has been shown to cause chronic inflammation, leading to the progression of various diseases. ANGPTL2 is known to exert cellular effects via receptors such as integrin α5ß1 and leukocyte immunoglobulin-like receptor subfamily B member 2 (LILRB2); however, their roles in ANGPTL2-induced inflammation remain unclear. In this study, we investigated the mechanisms underlying ANGPTL2-induced inflammation involving LILRB2 and various signaling pathways in human fibroblast-like synoviocytes (HFLS). The effects of ANGPTL2 and an anti-LILRB2 antibody on the gene expression of various inflammation-related factors were examined using real-time RT-PCR, while their effects on MAPK, NF-κB, and Akt phosphorylation were analyzed by western blotting. We found that the addition of ANGPTL2 enhanced the gene expression of inflammatory factors, whereas pretreatment with the anti-LILRB2 antibody for 12 h decreased the expression of these factors. Similarly, ANGPTL2 addition activated the phosphorylation of ERK, p38, JNK, NF-κB, and Akt in HFLS; however, this effect was significantly inhibited by pretreatment with the anti-LILRB2 antibody. Together, the findings of this study demonstrate that ANGPTL2 induces the expression of inflammatory factors via LILRB2 in synovial cells. Therefore, LILRB2 could be a potential therapeutic agent for treating matrix degradation in osteoarthritis.

Laryngeal Synovial Sarcoma: A Systematic Review of the Last 40 Years of Reported Cases.

Primary laryngeal synovial sarcoma is an extremely rare tumor predominantly affecting young adults. There are currently no well-defined guidelines to direct investigation and management, and treatment is largely based on what is known for synovial sarcoma of the upper and lower limbs. This PROSPERO-registered study aims to review the diagnostic methods, treatment regimens, and survival outcomes for patients with synovial sarcoma of the larynx. A systematic search of databases Medline, Embase, SCOPUS, and Web of Science was undertaken in December 2017. The literature search identified 1031 potentially relevant studies, and after the deletion of duplicates and excluded papers, 98 full-text articles were screened. A total of 39 cases were reviewed from 32 studies in the data extraction. The average age at the time of laryngeal synovial sarcoma diagnosis was 32 years (range, 11-79 years). In all cases (n = 39), patients underwent wide surgical excision, with 20 patients requiring a partial or total laryngectomy. A total of 18 patients received adjuvant and 3 received neoadjuvant radiotherapy. Chemotherapy was used in 10 cases, with ifosfamide the most frequently used agent. There was considerable variability in the order and combinations of the abovementioned treatments. No clinicopathologic factors or treatment regimens were associated with improved overall survival or lower rate of recurrence. There is a paucity of literature and heterogeneity in clinical approaches to this highly aggressive sarcoma. Reporting of cases must be standardized and formal guidelines must be established to guide clinical management.

Effect of mechanical injury and IL-1ß on the expression of LOXs and MMP-1, 2, 3 in PCL fibroblasts after co-culture with synoviocytes.

BACKGROUND: Crosstalk between posterior cruciate ligament fibroblasts (PCLfs) and synoviocytes (SCs) significantly modifies the homeostatic balance of the extracellular matrix (ECM) and appears to post a prominent affection for wound healing of PCL. Interleukin-1ß (IL-1ß) is regarded as a critical factor in acute inflammatory events during ligament injury. METHODS: In order to confirm the capability of SCs the response of lysyl oxidases (LOXs) and matrix metalloproteinases (MMPs) to IL-1ß, the complex cues of the joint cavity following PCL injury were simulated and the effect of IL-1ß on the expression of LOXs and MMPs in PCLfs were investigated. PCLfs in both the mono- and co-culture conditions were treated with IL-1ß. Cell lysates were collected from the PCLfs and LOXs and MMP-1, 2, 3 expression quantified using quantitative real-time PCR and western bolting. RESULTS: The results indicated that injury alone elevated the expression of LOXs and MMP-1, 2 and 3. But IL-1ß significantly decreased the LOX, LOXL1, and LOXL3 expression, and simultaneously increased MMP-1, 2 and 3 expressions in injured PCLfs. Furthermore, co-culture further suppressed LOXs, but stimulated MMP-1, 2 and 3 expressions when subjected to both mechanical injury and IL-1ß treatment. This possibly suggests that a number of soluble factors are secreted that act as mediators that amplify the response of SCs. CONCLUSION: The results indicated that the SCs could affect the IL-1ß-induction of LOXs inhibition and MMPs accumulation, which may be the underlying mechanism of the the poor healing response following PCL injury.

Invasion of Mycoplasma bovis into bovine synovial cells utilizing the clathrin-dependent endocytosis pathway.

Mycoplasma bovis causes chronic arthritis in cattle, accompanied by a severe inflammatory reaction of the joints. Recent studies demonstrated that M. bovis can invade bovine non-phagocytic cells, but the mechanism of M. bovis internalization in the cells remains unclear. In this study, we examined the mechanism by which M. bovis invades synovial cells, including the pathway of cell invasion. Using fluorescence and electron microscopy, multiple M. bovis were observed to adhere to and be internalized in cultured bovine synovial cells. The number of M. bovis colocalized with clathrin heavy chain (CLTC) per cell was significantly higher than the number of M. bovis colocalized with caveolin-1 (Cav-1). The internalized ratio of M. bovis in synovial cells treated with clathrin-dependent endocytosis inhibitor and small interfering RNA (siRNA) against CLTC was significantly lower than that in control cells. In contrast, the internalized ratio of M. bovis in synovial cells was unaffected by siRNA against Cav-1. These findings provide the first evidence that clathrin-dependent endocytosis is one of the major pathways by which M. bovis invades into synovial cells.