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BMC Genomics Apr 2024Unraveling the intricate and tightly regulated process of adipogenesis, involving coordinated activation of transcription factors and signaling pathways, is essential...
BACKGROUND
Unraveling the intricate and tightly regulated process of adipogenesis, involving coordinated activation of transcription factors and signaling pathways, is essential for addressing obesity and related metabolic disorders. The molecular pathways recruited by mesenchymal stem cells (MSCs) during adipogenesis are also dependent on the different sources of the cells and genetic backgrounds of donors, which contribute to the functional heterogeneity of the stem cells and consequently affect the developmental features and fate of the cells.
METHODS
In this study, the alteration of transcripts during differentiation of synovial mesenchymal stem cells (SMSCs) derived from fibrous synovium (FS) and adipose synovial tissue (FP) of two pig breeds differing in growth performance (German Landrace (DL)) and fat deposition (Angeln Saddleback (AS)) was investigated. SMSCs from both tissues and breeds were stimulated to differentiate into adipocytes in vitro and sampled at four time points (day 1, day 4, day 7 and day 14) to obtain transcriptomic data.
RESULTS
We observed numerous signaling pathways related to the cell cycle, cell division, cell migration, or cell proliferation during early stages of adipogenesis. As the differentiation process progresses, cells begin to accumulate intracellular lipid droplets and changes in gene expression patterns in particular of adipocyte-specific markers occur. PI3K-Akt signaling and metabolic pathways changed most during adipogenesis, while p53 signaling and ferroptosis were affected late in adipogenesis. When comparing MSCs from FS and FP, only a limited number of differentially expressed genes (DEGs) and enriched signaling pathways were identified. Metabolic pathways, including fat, energy or amino acid metabolism, were highly enriched in the AS breed SMSCs compared to those of the DL breed, especially at day 7 of adipogenesis, suggesting retention of the characteristic metabolic features of their original source, demonstrating donor memory in culture. In contrast, the DL SMSCs were more enriched in immune signaling pathways.
CONCLUSIONS
Our study has provided important insights into the dynamics of adipogenesis and revealed metabolic shifts in SMSCs associated with different cell sources and genetic backgrounds of donors. This emphasises the critical role of metabolic and genetic factors as important indications and criteria for donor stem cell selection.
Topics: Animals; Adipogenesis; Mesenchymal Stem Cells; Swine; Signal Transduction; Cell Differentiation; Gene Expression Profiling; Transcriptome; Synovial Membrane; Adipocytes; Cells, Cultured; Breeding
PubMed: 38664635
DOI: 10.1186/s12864-024-10308-z -
Clinical and Experimental Medicine Apr 2024The study of neuroimmune crosstalk and the involvement of neurotransmitters in inflammation and bone health has illustrated their significance in joint-related...
The study of neuroimmune crosstalk and the involvement of neurotransmitters in inflammation and bone health has illustrated their significance in joint-related conditions. One important mode of cell-to-cell communication in the synovial fluid (SF) is through extracellular vesicles (EVs) carrying microRNAs (miRNAs). The role of neurotransmitter receptors in the pathogenesis of inflammatory joint diseases, and whether there are specific miRNAs regulating differentially expressed HTR2A, contributing to the inflammatory processes and bone metabolism is unclear. Expression of neurotransmitter receptors and their correlated inflammatory molecules were identified in rheumatoid arthritis (RA) and osteoarthritis (OA) synovium from a scRNA-seq dataset. Immunohistochemistry staining of synovial tissue (ST) from RA and OA patients was performed for validation. Expression of miRNAs targeting HTR2A carried by SF EVs was screened in low- and high-grade inflammation RA from a public dataset and validated by qPCR. HTR2A reduction by target miRNAs was verified by miRNAs mimics transfection into RA fibroblasts. HTR2A was found to be highly expressed in fibroblasts derived from RA synovial tissue. Its expression showed a positive correlation with the degree of inflammation observed. 5 miRNAs targeting HTR2A were decreased in RA SF EVs compared to OA, three of which, miR-214-3p, miR-3120-5p and miR-615-3p, mainly derived from monocytes in the SF, were validated as regulators of HTR2A expression. The findings suggest that fibroblast HTR2A may play a contributory role in inflammation and the pathogenesis of RA. Additionally, targeting miRNAs that act upon HTR2A could present novel therapeutic strategies for alleviating inflammation in RA.
Topics: Humans; Arthritis, Rheumatoid; Extracellular Vesicles; Fibroblasts; Gene Expression Regulation; Inflammation; MicroRNAs; Osteoarthritis; Receptor, Serotonin, 5-HT2A; Synovial Fluid; Synovial Membrane
PubMed: 38662111
DOI: 10.1007/s10238-024-01352-w -
Cureus Mar 2024Within the synovial membrane, cartilaginous nodules form as a result of a relatively rare joint condition called synovial chondromatosis. This case study describes the...
Within the synovial membrane, cartilaginous nodules form as a result of a relatively rare joint condition called synovial chondromatosis. This case study describes the open surgical treatment of a male patient, age 25, who had severe discomfort in his right knee. The patient had synovial chondromatosis. The choice for open surgery was made because of the large and difficult nature of the lesions, even though arthroscopic procedures are commonly used in the management of this problem. The patient's history included a restricted range of motion, edema, and chronic right knee discomfort. Multiple intra-articular loose bodies were discovered during the clinical examination and imaging examinations, which led to the decision to do surgery. Owing to the size and position of the chondromatous lesions, an open surgical technique was considered suitable. Given the favorable result in this young adult patient, open surgical management of synovial chondromatosis may be an effective treatment option, especially in cases with complicated or widespread involvement.
PubMed: 38659563
DOI: 10.7759/cureus.56901 -
Journal of Nanobiotechnology Apr 2024Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by synovial inflammation, causing substantial disability and reducing life quality. While...
BACKGROUND
Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by synovial inflammation, causing substantial disability and reducing life quality. While macrophages are widely appreciated as a master regulator in the inflammatory response of RA, the precise mechanisms underlying the regulation of proliferation and inflammation in RA-derived fibroblast-like synoviocytes (RA-FLS) remain elusive. Here, we provide extensive evidence to demonstrate that macrophage contributes to RA microenvironment remodeling by extracellular vesicles (sEVs) and downstream miR-100-5p/ mammalian target of rapamycin (mTOR) axis.
RESULTS
We showed that bone marrow derived macrophage (BMDM) derived-sEVs (BMDM-sEVs) from collagen-induced arthritis (CIA) mice (cBMDM-sEVs) exhibited a notable increase in abundance compared with BMDM-sEVs from normal mice (nBMDM-sEVs). cBMDM-sEVs induced significant RA-FLS proliferation and potent inflammatory responses. Mechanistically, decreased levels of miR-100-5p were detected in cBMDM-sEVs compared with nBMDM-sEVs. miR-100-5p overexpression ameliorated RA-FLS proliferation and inflammation by targeting the mTOR pathway. Partial attenuation of the inflammatory effects induced by cBMDM-sEVs on RA-FLS was achieved through the introduction of an overexpression of miR-100-5p.
CONCLUSIONS
Our work reveals the critical role of macrophages in exacerbating RA by facilitating the transfer of miR-100-5p-deficient sEVs to RA-FLS, and sheds light on novel disease mechanisms and provides potential therapeutic targets for RA interventions.
Topics: Animals; Humans; Male; Mice; Arthritis, Experimental; Arthritis, Rheumatoid; Cell Proliferation; Extracellular Vesicles; Inflammation; Macrophages; Mice, Inbred DBA; MicroRNAs; Signal Transduction; Synovial Membrane; Synoviocytes; TOR Serine-Threonine Kinases
PubMed: 38644475
DOI: 10.1186/s12951-024-02444-1 -
Reumatologia Clinica Apr 2024The characteristics of synovial fluid (SF) in geriatric patients differ from those in younger patients. In Mexico, epidemiologic data on the incidence of different...
BACKGROUND
The characteristics of synovial fluid (SF) in geriatric patients differ from those in younger patients. In Mexico, epidemiologic data on the incidence of different rheumatic diseases in geriatric patients are scarce.
OBJECTIVE
To describe the physical characteristics of geriatric SF and the prevalence of crystals in knee and other joint aspirates from patients with previously diagnosed joint disease.
MATERIALS AND METHODS
A retrospective study was performed with a baseline of 517 SF samples between 2011 and 2023. White blood cell count was performed by Neubauer chamber and crystals were identified by polarized light microscopy. Descriptive statistical analysis was performed and prevalence was reported as a percentage.
RESULTS
The mean age of the adults was 73.5±5.0 years, 54.4% were women and 45.6% were men. The mean SF volume was 6.3±9.5mL in older adults and 15.3±24.9mL in those younger than 65 years. The mean viscosity in older adults was 9.5±4.5mm and the mean leukocyte count was 7352±16,402leukocytes/mm. Seventy percent of the older adults' SFs were referred to the laboratory for osteoarthritis (OA), with lower proportions for rheumatoid arthritis (RA) (14.6%) and gout (5.1%). Of the crystals observed in the geriatric population, 14.6% corresponded to monosodium urate crystals (CUM) and 18.9% to calcium pyrophosphate crystals (CPP).
CONCLUSIONS
The characteristics of LS in older adults were smaller volume, increased viscosity, and non-inflammatory. The main diagnoses were OA, RA, and gout. The crystal content of the SF of the geriatric population corresponded mainly to CPP.
Topics: Humans; Synovial Fluid; Aged; Male; Female; Retrospective Studies; Middle Aged; Gout; Aged, 80 and over; Arthritis, Rheumatoid; Mexico; Leukocyte Count; Age Factors
PubMed: 38644030
DOI: 10.1016/j.reumae.2023.12.009 -
Cartilage Apr 2024Exosomes derived from bone marrow mesenchymal stem cells (BMSC-Exos) may modulate the M1/M2 polarization of macrophages during osteoarthritis (OA). However, the...
OBJECTIVE
Exosomes derived from bone marrow mesenchymal stem cells (BMSC-Exos) may modulate the M1/M2 polarization of macrophages during osteoarthritis (OA). However, the underlying mechanisms of BMSC-Exos in this process still need to be elucidated. In this study, we explored the role of BMSC-Exos in the polarization of macrophages and the OA rats .
METHODS
The effects of BMSC-Exos on RAW264.7 cells were determined, including the production of reactive oxygen species (ROS) and the protein expression of Akt, PINK1, and Parkin. We prepared an OA model by resecting the anterior cruciate ligament and medial meniscus of Sprague-Dawley (SD) rats. Hematoxylin-eosin (H&E) and safranin O-fast green staining, immunohistochemistry and immunofluorescence analyses, and the examination of interleukin 6 (IL-6), interleukin 1β (IL-1β), tumor necrosis factor alpha (TNF-α), and interleukin 10 (IL-10) were performed to assess changes in cartilage and synovium.
RESULTS
BMSC-Exos inhibited mitochondrial membrane damage, ROS production, and the protein expression of PINK1 and Parkin. Akt phosphorylation was downregulated under lipopolysaccharide (LPS) induction but significantly recovered after treatment with BMSC-Exos. BMSC-Exos alleviated cartilage damage, inhibited M1 polarization, and promoted M2 polarization in the synovium in OA rats. The expression of PINK1 and Parkin in the synovium and the levels of IL-6, IL-1β, and TNF-α in the serum decreased, but the level of IL-10 increased when BMSC-Exos were used in OA rats.
CONCLUSION
BMSC-Exos ameliorate OA development by regulating synovial macrophage polarization, and one of the underlying mechanisms may be through inhibiting PINK1/Parkin signaling.
PubMed: 38641989
DOI: 10.1177/19476035241245805 -
Medicine Apr 2024An increase in CD4+ T cells in the synovium is closely linked to the pathogenesis of rheumatoid arthritis (RA). We aimed to identify the possible causes of the elevated...
An increase in CD4+ T cells in the synovium is closely linked to the pathogenesis of rheumatoid arthritis (RA). We aimed to identify the possible causes of the elevated CD4+ T cell levels and to explore the factors influencing disease activity in RA. Fifty-five RA patients, including 28 with active RA (ARA), 27 with inactive RA, and 22 healthy controls, were recruited for this study. The proportion of CCR9+CD4+ T cells and the expression of chemokine receptor 9 (CCR9) on CD4+ T cells were analyzed by flow cytometry. Enzyme-linked immunosorbent assay and chemiluminescent immunoassay were used to evaluate interleukin (IL)-17A and IL-6 levels, respectively. The proportion of CCR9+CD4+ T cells and the expression of CCR9 on CD4+ T cells increased significantly in peripheral blood (PB) and synovial fluid (SF) in ARA compared to those in inactive RA. Furthermore, SF contained more CCR9+CD4+ T cells, IL-6, and IL-17A than PB in RA patients. Moreover, CD4+ T cells in the PB of patients with RA, especially ARA, expressed more CCR9 and secreted more IL-6 and IL-17A after activation. Here, we also demonstrated that both the percentage of CCR9+ cells in CD4+ T cells and the expression of CCR9 on circulating CD4+ T cells were positively correlated with erythrocyte sedimentation rate, hypersensitive C-reactive protein, rheumatoid factor, and anti-cyclic citrullinated peptide antibody. CCR9+CD4+ T cells are elevated in PB and SF, and are associated with disease activity in patients with RA.
Topics: Humans; Arthritis, Rheumatoid; CD4-Positive T-Lymphocytes; Interleukin-17; Interleukin-6; Receptors, Chemokine; Synovial Fluid
PubMed: 38640336
DOI: 10.1097/MD.0000000000037803 -
European Review For Medical and... Apr 2024Synovial chondromatosis is a non-malignant synovial disorder characterized by the presence of cartilage formation within the synovial membrane, leading to the emergence... (Review)
Review
BACKGROUND
Synovial chondromatosis is a non-malignant synovial disorder characterized by the presence of cartilage formation within the synovial membrane, leading to the emergence of multiple cartilaginous nodules that may be either attached or unattached. The presence of this anatomical feature is frequently observed in articulations such as the knee, hip, elbow, and ankle.
CASE REPORT
In this study, we present a case of synovial chondromatosis in the knee joint of a healthy male in his early 60s. Notably, the patient exhibited the simultaneous presence of 87 large loose bodies. The occurrence of a substantial quantity of unattached entities of notable dimensions within the joint is highly uncommon.
CONCLUSIONS
The patient had several synovial chondromas, a rare disease. Synovial chondromatosis is a benign disorder; however, growing synovium can cause pyogenic cartilage nodules. Most loose bodies in joints can abrade and degenerate articular cartilage, causing long-term discomfort. Thus, an early-stage procedure to remove loose bodies and carefully excise synovial tissue is necessary to treat this condition.
Topics: Humans; Male; Ankle Joint; Cartilage, Articular; Chondromatosis, Synovial; Knee Joint; Synovial Membrane; Middle Aged
PubMed: 38639506
DOI: 10.26355/eurrev_202404_35895 -
Scientific Reports Apr 2024Total knee arthroplasty (TKA) is an effective procedure for pain relief; however, the emergence of postsurgical pain remains a concern. In this study, we investigated...
Total knee arthroplasty (TKA) is an effective procedure for pain relief; however, the emergence of postsurgical pain remains a concern. In this study, we investigated the production of nerve growth factor (NGF) and mediators that affect NGF production and their function in the synovial fluid and plasma after TKA. This study included 19 patients (20 knees) who had rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and knee osteoarthritis (OA) who underwent TKA, categorized into OA and non-OA groups. The levels of NGF, inflammatory cytokines, and lipid mediators were analyzed before and after surgery. The intraoperative synovial fluid NGF concentration was more than seven times higher in the non-OA group than in the OA group. The intra-articular NGF levels increased significantly by more than threefold postoperatively in the OA group but not in the non-OA group. Moreover, the levels of inflammatory cytokines and lipid mediators were increased in the synovial fluid of both groups. The intra-articular cytokines or NGF concentrations positively correlated with postoperative pain. Targeted NGF control has the potential to alleviate postsurgical pain in TKA, especially in patients with OA, emphasizing the importance of understanding NGF dynamics under different knee conditions.
Topics: Humans; Arthroplasty, Replacement, Knee; Synovial Fluid; Nerve Growth Factor; Osteoarthritis, Knee; Pain, Postoperative; Cytokines; Lipids
PubMed: 38637604
DOI: 10.1038/s41598-024-59685-1 -
Journal of Nanobiotechnology Apr 2024Rheumatoid arthritis (RA) is a progressive autoimmune disease accompanied by joint swelling, cartilage erosion and bone damage. Drug therapy for RA has been restricted...
Synovium microenvironment-responsive injectable hydrogel inducing modulation of macrophages and elimination of synovial fibroblasts for enhanced treatment of rheumatoid arthritis.
Rheumatoid arthritis (RA) is a progressive autoimmune disease accompanied by joint swelling, cartilage erosion and bone damage. Drug therapy for RA has been restricted due to poor therapeutic effect, recurrence and adverse effects. Macrophages and synovial fibroblasts both play important roles in the pathology of RA. Macrophages secrete large amount of pro-inflammatory cytokines, while synovial fibroblasts are tightly correlated with hypoxia synovium microenvironment, cytokine release, recruitment of pro-inflammatory cells, bone and cartilage erosion. Therefore, in this timely research, an injectable and pH-sensitive peptide hydrogel loading methotrexate (MTX) and bismuthene nanosheet/polyethyleneimine (BiNS/PEI) has been developed to reduce the activity of macrophages and eliminate over-proliferated synovial fibroblasts simultaneously. MTX can reduce the cytokine secretion of macrophages/anti-apoptosis property of synovial fibroblasts and BiNS/PEI can eliminate synovial fibroblasts via photodynamic therapy (PDT) and photothermal therapy (PTT) routes. The hydrogel was injected into the acidic inflammatory synovium for precise targeting and served as a drug reservoir for pH responsive and sustained drug release, while improving the bioavailability and reducing the toxicity of MTX. Excellent therapeutic efficacy has been achieved in both in vivo and in vitro studies, and this unique drug delivery system provides a new and robust strategy to eliminate synovial fibroblasts and modulate immune system for RA treatment in clinical.
Topics: Humans; Hydrogels; Arthritis, Rheumatoid; Synovial Membrane; Macrophages; Methotrexate; Cytokines; Fibroblasts
PubMed: 38632657
DOI: 10.1186/s12951-024-02465-w