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Nature Communications Jun 2024Rheumatoid arthritis (RA) is an autoimmune disease involving antigen-specific T and B cells. Here, we perform single-cell RNA and repertoire sequencing on paired...
Rheumatoid arthritis (RA) is an autoimmune disease involving antigen-specific T and B cells. Here, we perform single-cell RNA and repertoire sequencing on paired synovial tissue and blood samples from 12 seropositive RA patients. We identify clonally expanded CD4 + T cells, including CCL5+ cells and T peripheral helper (Tph) cells, which show a prominent transcriptomic signature of recent activation and effector function. CD8 + T cells show higher oligoclonality than CD4 + T cells, with the largest synovial clones enriched in GZMK+ cells. CD8 + T cells with possibly virus-reactive TCRs are distributed across transcriptomic clusters. In the B cell compartment, NR4A1+ activated B cells, and plasma cells are enriched in the synovium and demonstrate substantial clonal expansion. We identify synovial plasma cells that share BCRs with synovial ABC, memory, and activated B cells. Receptor-ligand analysis predicted IFNG and TNFRSF members as mediators of synovial Tph-B cell interactions. Together, these results reveal clonal relationships between functionally distinct lymphocyte populations that infiltrate the synovium of patients with RA.
Topics: Humans; Arthritis, Rheumatoid; Synovial Membrane; B-Lymphocytes; Female; Male; Middle Aged; CD8-Positive T-Lymphocytes; Lymphocyte Subsets; CD4-Positive T-Lymphocytes; Single-Cell Analysis; Transcriptome; Plasma Cells; Aged; Lymphocyte Activation; Adult
PubMed: 38862501
DOI: 10.1038/s41467-024-49186-0 -
RMD Open Jun 2024To assess the presence and anatomical distribution of activated fibroblasts in the joints and entheses of patients with psoriasis with arthralgia and to test how...
OBJECTIVES
To assess the presence and anatomical distribution of activated fibroblasts in the joints and entheses of patients with psoriasis with arthralgia and to test how fibroblast activation visualised by gallium-labelled fibroblast activation protein inhibitor-04 (Ga-FAPI-04)-positron emission tomography (PET)/CT correlates with clinical tenderness, musculoskeletal ultrasound findings and progression to psoriatic arthritis (PsA).
METHODS
We conducted a prospective cohort study in patients with psoriasis and arthralgia who underwent clinical and ultrasound evaluation and whole-body PET/CT imaging with Ga-FAPI-04. Ga-FAPI-04 uptake at synovial and entheseal sites was assessed by maximal standardised uptake values (SUVmax) and PET/CT Joint Index (JI); logistic regression models were used to investigate its correlation with clinical and ultrasound findings. Survival analyses were performed on patients with at least 6 months of follow-up.
RESULTS
36 patients with psoriasis were enrolled. Ga-FAPI-04 uptake was found in 318 (7.9%) joints and 369 (7.3%) entheses in 29 (80.6%) participants, with a mean SUVmax (SD) of 3.2 (1.8) for joints and 2.9 (1.6) for entheses. Large joints and the lower limbs were predominantly affected. A significant positive relationship was found between Ga-FAPI-04-PET/CT signal intensity and the 68 tender joint count (SUVmax: p<0.001; PET/CT-JI: p<0.001) and tender entheses count (SUVmax: p<0.001; PET/CT-JI: p=0.002). No correlations were found with ultrasound findings (SUVmax: p=0.969; PET/CT-JI: p=0.720). Patients with relevant synovio-entheseal Ga-FAPI-04 uptake showed a statistically significant higher risk of developing PsA (p=0.02), independent of ultrasound findings.
CONCLUSIONS
Patients with psoriasis presenting with arthralgia show localised signs of resident tissue activation in joints and entheses, which are associated with higher risk of developing PsA.
Topics: Humans; Arthritis, Psoriatic; Male; Female; Middle Aged; Positron Emission Tomography Computed Tomography; Psoriasis; Adult; Prospective Studies; Fibroblasts; Synovial Membrane; Aged; Ultrasonography; Disease Progression
PubMed: 38862244
DOI: 10.1136/rmdopen-2024-004294 -
Cureus May 2024Chronic unreduced dislocations of the proximal interphalangeal joint are uncommon, and management principles for these injuries have not been defined. The dislocation...
Chronic unreduced dislocations of the proximal interphalangeal joint are uncommon, and management principles for these injuries have not been defined. The dislocation can be volar or dorsal and closed reduction is rarely successful owing to soft tissue contractures. Treatment options in literature reviews for such rare injuries included open reduction of pip joint with volar plate arthroplasty, extension block pinning, hemi hamate arthroplasty, pip joint arthrodesis, Suzuki dynamic frame fixation, open reduction and repair of capsule and collateral ligaments with suture anchors. Few cases of amputation following treatment were even reported in literature emphasizing the role of meticulous soft tissue handling in such neglected cases of hand. We report six cases of neglected (more than three months old) dorsal dislocation of the PIP joint of the hand, treated with volar plate arthroplasty and extension block pinning. A functional range of motion with a stable joint can be achieved in such injuries with volar plate arthroplasty, as long as the articular cartilage is relatively preserved and bone loss is <30%.
PubMed: 38860079
DOI: 10.7759/cureus.60077 -
Nature Reviews. Rheumatology Jul 2024Joint kinematic instability, arising from congenital or acquired musculoskeletal pathoanatomy or from imbalances in anabolism and catabolism induced by... (Review)
Review
Joint kinematic instability, arising from congenital or acquired musculoskeletal pathoanatomy or from imbalances in anabolism and catabolism induced by pathophysiological factors, leads to deterioration of the composition, structure and function of cartilage and, ultimately, progression to osteoarthritis (OA). Alongside articular cartilage degeneration, synovial fluid lubricity decreases in OA owing to a reduction in the concentration and molecular weight of hyaluronic acid and surface-active mucinous glycoproteins that form a lubricating film over the articulating joint surfaces. Minimizing friction between articulating joint surfaces by lubrication is fundamental for decreasing hyaline cartilage wear and for maintaining the function of synovial joints. Augmentation with highly viscous supplements (that is, viscosupplementation) offers one approach to re-establishing the rheological and tribological properties of synovial fluid in OA. However, this approach has varied clinical outcomes owing to limited intra-articular residence time and ineffective mechanisms of chondroprotection. This Review discusses normal hyaline cartilage function and lubrication and examines the advantages and disadvantages of various strategies for restoring normal joint lubrication. These strategies include contemporary viscosupplements that contain antioxidants, anti-inflammatory drugs or platelet-rich plasma and new synthetic synovial fluid additives and cartilage matrix enhancers. Advanced biomimetic tribosupplements offer promise for mitigating cartilage wear, restoring joint function and, ultimately, improving patient care.
Topics: Humans; Viscosupplementation; Osteoarthritis; Hyaluronic Acid; Cartilage, Articular; Viscosupplements; Synovial Fluid; Dietary Supplements
PubMed: 38858605
DOI: 10.1038/s41584-024-01125-5 -
JPRAS Open Jun 2024A synovial cyst is a herniation of synovial tissue through a joint capsule, often mistaken for a ganglion cyst. The key distinctions are that synovial cysts have a...
BACKGROUND
A synovial cyst is a herniation of synovial tissue through a joint capsule, often mistaken for a ganglion cyst. The key distinctions are that synovial cysts have a synovial cell lining, while a ganglion cyst is delineated by dense fibrous connective tissue. Typically found near joints, synovial cysts are associated with conditions like osteoarthritis, prevalent in females aged 20 to 50. We present a rare case of a synovial cyst in the extensor digitorum superficialis of the right hand.
CASE SUMMARY
A 53-year-old Hispanic female visited our hand clinic due to a 3-year history of pain on the back of her right hand. At exploration, a 3 × 3 cm soft tumor was identified. Surgery revealed a clear-yellowish mass within the extensor digitorum superficialis tendon. Following the surgery, synovial cyst was confirmed by pathology and the patient was discharged without complications.
CONCLUSION
This case highlights the rare presentation of an intratendinous synovial cyst and emphasizes the importance of a comprehensive understanding of synovial cysts in the differential diagnosis of hand tumors.
PubMed: 38854624
DOI: 10.1016/j.jpra.2024.02.014 -
Journal of Hand and Microsurgery Mar 2024The standard treatment for mucous cysts with Heberden nodes is excision of the dorsolateral osteophytes and capsule of the distal interphalangeal joint or thumb...
The standard treatment for mucous cysts with Heberden nodes is excision of the dorsolateral osteophytes and capsule of the distal interphalangeal joint or thumb interphalangeal joint, including the stalk of the cyst. The skin incision varies for cases depending upon the geometry. We propose a surgical method utilizing blind lateral approaches for treating such mucous cysts.
PubMed: 38854384
DOI: 10.1055/s-0043-1761228 -
European Journal of Radiology Jul 2024To assess the accuracy of 0.55 T MRI in diagnosing periprosthetic joint infection (PJI) in patients with symptomatic total hip arthroplasty (THA).
PURPOSE
To assess the accuracy of 0.55 T MRI in diagnosing periprosthetic joint infection (PJI) in patients with symptomatic total hip arthroplasty (THA).
MATERIAL AND METHODS
0.55 T MRI of patients with THA PJI (Group A) and noninfected THA (Group B), including aseptic loosening (Group C, subgroup of B) performed between May 2021 and July 2023 were analysed retrospectively. Two musculoskeletal fellowship-trained radiologists independently identified MRI bone and soft tissue changes including: marrow oedema, periosteal reaction, osteolysis, joint effusion, capsule oedema and thickening, fluid collections, muscle oedema, bursitis, inguinal adenopathy, and muscle tears. The diagnostic performance of MRI discriminators of PJI was evaluated using Fisher's exact test (p < 0.05) and interrater reliability was determined. 61 MRI scans from 60 THA patients (34 female, median age 68, range 41-93 years) in Group A (n = 9; female 4; median age 69, range 56-82 years), B (n = 51; 30; 67.5, 41-93 years), and C (10; 6; 67; 41-82 years) were included.
RESULTS
Capsule oedema (sensitivity 89 %, specificity 92 %,), intramuscular oedema (89 %, 82 %) and joint effusion (89 %, 73 %) were the best performing discriminators for PJI diagnosis (p ≤ 0.001), when viewed individually and had combined 70 % sensitivity and 100 % specificity for PJI diagnosis in parallel testing. For the differentiation between PJI and aseptic loosening, intramuscular oedema (89 %, 80 %) and capsule oedema (89 %, 80 %) were significant discriminators (p ≤ 0.001) with combined 64 % sensitivity and 96 % specificity for PJI.
CONCLUSIONS
New generation 0.55 T MRI may aid in the detection of PJI in symptomatic patients. Oedema of the joint capsule, adjacent muscles as well as joint effusion were indicative of the presence of PJI.
Topics: Humans; Female; Male; Aged; Magnetic Resonance Imaging; Prosthesis-Related Infections; Middle Aged; Aged, 80 and over; Adult; Reproducibility of Results; Retrospective Studies; Sensitivity and Specificity; Arthroplasty, Replacement, Hip; Hip Prosthesis; Hip Joint
PubMed: 38851014
DOI: 10.1016/j.ejrad.2024.111524 -
Frontiers in Immunology 2024Pathological changes in the articular cartilage (AC) and synovium are major manifestations of osteoarthritis (OA) and are strongly associated with pain and functional...
Exosomes derived from miR-146a-overexpressing fibroblast-like synoviocytes in cartilage degradation and macrophage M1 polarization: a novel protective agent for osteoarthritis?
INTRODUCTION
Pathological changes in the articular cartilage (AC) and synovium are major manifestations of osteoarthritis (OA) and are strongly associated with pain and functional limitations. Exosome-derived microRNAs (miRNAs) are crucial regulatory factors in intercellular communication and can influence the progression of OA by participating in the degradation of chondrocytes and the phenotypic transformation in the polarization of synovial macrophages. However, the specific relationships and pathways of action of exosomal miRNAs in the pathological progression of OA in both cartilage and synovium remain unclear.
METHODS
This study evaluates the effects of fibroblast-like synoviocyte (FLS)-derived exosomes (FLS-Exos), influenced by miR-146a, on AC degradation and synovial macrophage polarization. We investigated the targeted relationship between miR-146a and TRAF6, both and , along with the involvement of the NF-κB signaling pathway.
RESULTS
The expression of miR-146a in the synovial exosomes of OA rats was significantly higher than in healthy rats. , the upregulation of miR-146a reduced chondrocyte apoptosis, whereas its downregulation had the opposite effect. , exosomes derived from miR-146a-overexpressing FLSs (miR-146a-FLS-Exos) reduced AC injury and chondrocyte apoptosis in OA. Furthermore, synovial proliferation was reduced, and the polarization of synovial macrophages shifted from M1 to M2. Mechanistically, the expression of TRAF6 was inhibited by targeting miR-146a, thereby modulating the Toll-like receptor 4/TRAF6/NF-κB pathway in the innate immune response.
DISCUSSION
These findings suggest that miR-146a, mediated through FLS-Exos, may alleviate OA progression by modulating cartilage degradation and macrophage polarization, implicating the NF-κB pathway in the innate immune response. These insights highlight the therapeutic potential of miR-146a as a protective agent in OA, underscoring the importance of exosomal miRNAs in the pathogenesis and potential treatment of the disease.
Topics: MicroRNAs; Animals; Exosomes; Osteoarthritis; Rats; Macrophages; Synoviocytes; Male; TNF Receptor-Associated Factor 6; Cartilage, Articular; Chondrocytes; NF-kappa B; Signal Transduction; Rats, Sprague-Dawley; Fibroblasts; Synovial Membrane; Cells, Cultured; Apoptosis; Toll-Like Receptor 4; Macrophage Activation
PubMed: 38846937
DOI: 10.3389/fimmu.2024.1361606 -
Cellular and Molecular Biology... Jun 2024GABBR1 receptors have been implicated in the progression of rheumatoid arthritis (RA), and p38 MAP kinase (MAPK) was shown to be downregulated by GABA and result in...
GABBR1 receptors have been implicated in the progression of rheumatoid arthritis (RA), and p38 MAP kinase (MAPK) was shown to be downregulated by GABA and result in unchecked production of pro-inflammatory cytokine. GABBR1 is a member of GABA receptors, and it is known to be upregulated and plays a vital role in RA. Glucocorticoids are efficient therapeutics in rheumatoid arthritis (RA) and are known to regulate GABA actions; therefore, we intended to investigate the potential of glucocorticoids in RA concerning the potential pathway GABBR1/MAPK. Joint specimens were obtained from collagen-induced arthritis mouse model. A double-blind semi-quantitative analysis of vascularity, cell infiltration, as well as lining thickness by help of a 4-point scale setting was used to assess joint inflammation. Expression of GABBR1 and p38 was evaluated immunohistochemically. In vitro peripheral blood (PB), synovial fluid (SF), and mononuclear cells (MCs) were acquired from RA mice. Western blotting was used for detecting expression of GABBR1 and p38 proteins. The presence of high levels of GABBR1 and p38 was prevalent in RA joints relative to healthy joints and related to the inflammation level. Glucocorticoid treatment alters GABBR1 along with p38 protein expression in joints while reducing joint inflammation. Ex vivo and in vitro assays revealed glucocorticoids have a direct impact on p38, such as the decreased GABBR1 expression level after dexamethasone incubation with SFMC. GABBR1 together with p38 expression in RA joints depends on local inflammation and can be targeted by glucocorticoids.
Topics: Arthritis, Rheumatoid; Animals; Glucocorticoids; p38 Mitogen-Activated Protein Kinases; Arthritis, Experimental; Mice; Male; Joints; Mice, Inbred DBA; Synovial Fluid; Cellular Microenvironment; Leukocytes, Mononuclear; Disease Models, Animal
PubMed: 38836679
DOI: 10.14715/cmb/2024.70.6.12 -
Frontiers in Veterinary Science 2024Osteoartritis (OA) is a debilitating disease affecting both humans and animals. In the early stages, OA is characterized by damage to the extracellular matrix (ECM) and... (Review)
Review
Osteoartritis (OA) is a debilitating disease affecting both humans and animals. In the early stages, OA is characterized by damage to the extracellular matrix (ECM) and apoptosis and depletion of chondrocytes. OA progression is characterized by hyaline cartilage loss, chondrophyte and osteophyte formation, thickening of the joint capsule and function loss in the later stages. As the regenerative potential of cartilage is very limited and osteoarthritic changes are irreversible, prevention of OA, modulation of existing osteoarthritic joint inflammation, reducing joint pain and supporting joint function are the only options. Progression of OA and pain may necessitate surgical intervention with joint replacement or arthrodesis as end-stage procedures. In human medicine, the role of adipokines in the development and progression of OA has received increasing interest. At present, the known adipokines include leptin, adiponectin, visfatin, resistin, progranulin, chemerin, lipocalin-2, vaspin, omentin-1 and nesfatin. Adipokines have been demonstrated to play a pivotal role in joint homeostasis by modulating anabolic and catabolic balance, autophagy, apoptosis and inflammatory responses. In small animals, in terms of dogs and cats, naturally occurring OA has been clearly demonstrated as a clinical problem. Similar to humans, the etiology of OA is multifactorial and has not been fully elucidated. Humans, dogs and cats share many joint related degenerative diseases leading to OA. In this review, joint homeostasis, OA, adipokines and the most common joint diseases in small animals leading to naturally occurring OA and their relation with adipokines are discussed. The purpose of this review is highlighting the translational potential of OA and adipokines research in small animal patients.
PubMed: 38831954
DOI: 10.3389/fvets.2024.1193702