Browsing by Author "Semenistaja, Sofija"

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    Healthy and Osteoarthritis-Affected Joints Facing the Cellular Crosstalk
    (2023-02-18) Semenistaja, Sofija; Skuja, Sandra; Kadiša, Anda; Groma, Valērija; Department of Doctoral Studies; Joint Laboratory of Electron Microscopy; Institute of Anatomy and Anthropology; Department of Internal Diseases
    Osteoarthritis (OA) is a chronic, progressive, severely debilitating, and multifactorial joint disease that is recognized as the most common type of arthritis. During the last decade, it shows an incremental global rise in prevalence and incidence. The interaction between etiologic factors that mediate joint degradation has been explored in numerous studies. However, the underlying processes that induce OA remain obscure, largely due to the variety and complexity of these mechanisms. During synovial joint dysfunction, the osteochondral unit undergoes cellular phenotypic and functional alterations. At the cellular level, the synovial membrane is influenced by cartilage and subchondral bone cleavage fragments and extracellular matrix (ECM) degradation products from apoptotic and necrotic cells. These "foreign bodies" serve as danger-associated molecular patterns (DAMPs) that trigger innate immunity, eliciting and sustaining low-grade inflammation in the synovium. In this review, we explore the cellular and molecular communication networks established between the major joint compartments-the synovial membrane, cartilage, and subchondral bone of normal and OA-affected joints.
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    Inflammatory Cytokine-Producing Cells and Inflammation Markers in the Synovium of Osteoarthritis Patients Evidenced in Human Herpesvirus 7 Infection
    (2020) Groma, Valerija; Tarasovs, Mihails; Skuja, Sandra; Semenistaja, Sofija; Nora-Krukle, Zaiga; Svirskis, Simons; Murovska, Modra
    A direct association between joint inflammation and the progression of osteoarthritis (OA) has been proposed, and synovitis is considered a powerful driver of the disease. Among infections implicated in the development of joint disease, human herpesvirus 7 (HHV-7) infection remains poorly characterized. Therefore, we assessed synovitis in OA patients; determined the occurrence and distribution of the HHV-7 antigen within the synovial membrane of OA-affected subjects; and correlated plasma levels of the pro-inflammatory cytokines tumor necrosis factor (TNF), interleukin-6 (IL-6), and TNF expressed locally within lesioned synovial tissues with HHV-7 observations, suggesting differences in persistent latent and active infection. Synovial HHV-7, CD4, CD68, and TNF antigens were detected immunohistochemically. The plasma levels of TNF and IL-6 were measured by an enzyme-linked immunosorbent assay. Our findings confirm the presence of persistent HHV-7 infection in 81.5% and reactivation in 20.5% of patients. In 35.2% of patients, virus-specific DNA was extracted from synovial membrane tissue samples. We evidenced the absence of histopathologically detectable synovitis and low-grade changes in the majority of OA patients enrolled in the study, in both HHV-7 PCR+ and HHV-7 PCR‒ groups. The number of synovial CD4-positive cells in the HHV-7 polymerase chain reaction (PCR)+ group was significantly higher than that in the HHV-7 PCR‒ group. CD4- and CD68-positive cells were differently distributed in both HHV-7 PCR+ and HHV-7 PCR‒ groups, as well as in latent and active HHV-7 infection. The number of TNF+ and HHV-7+ lymphocytes, as well as HHV-7+ vascular endothelial cells, was strongly correlated. Vascular endothelial cells, especially in the case of infection reactivation, appeared vulnerable. The balance between virus latency and reactivation is a long-term relationship between the host and infectious agent, and the immune system appears to be involved in displaying overreaction when a shift in the established equilibrium develops.
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    Inflammatory cytokine-producing cells and inflammation markers in the synovium of osteoarthritis patients evidenced in human herpesvirus 7 infection
    (2020-09-01) Groma, Valerija; Tarasovs, Mihails; Skuja, Sandra; Semenistaja, Sofija; Nora-Krukle, Zaiga; Svirskis, Simons; Murovska, Modra; Joint Laboratory of Electron Microscopy; Institute of Anatomy and Anthropology; Department of Internal Diseases; Institute of Microbiology and Virology
    A direct association between joint inflammation and the progression of osteoarthritis (OA) has been proposed, and synovitis is considered a powerful driver of the disease. Among infections implicated in the development of joint disease, human herpesvirus 7 (HHV-7) infection remains poorly characterized. Therefore, we assessed synovitis in OA patients; determined the occurrence and distribution of the HHV-7 antigen within the synovial membrane of OA-affected subjects; and correlated plasma levels of the pro-inflammatory cytokines tumor necrosis factor (TNF), interleukin-6 (IL-6), and TNF expressed locally within lesioned synovial tissues with HHV-7 observations, suggesting differences in persistent latent and active infection. Synovial HHV-7, CD4, CD68, and TNF antigens were detected immunohistochemically. The plasma levels of TNF and IL6 were measured by an enzyme-linked immunosorbent assay. Our findings confirm the presence of persistent HHV-7 infection in 81.5% and reactivation in 20.5% of patients. In 35.2% of patients, virusspecific DNA was extracted from synovial membrane tissue samples. We evidenced the absence of histopathologically detectable synovitis and low-grade changes in the majority of OA patients enrolled in the study, in both HHV-7 PCR+ and HHV-7 PCR‒ groups. The number of synovial CD4positive cells in the HHV-7 polymerase chain reaction (PCR)+ group was significantly higher than that in the HHV-7 PCR‒ group. CD4-and CD68-positive cells were differently distributed in both HHV-7 PCR+ and HHV-7 PCR‒ groups, as well as in latent and active HHV-7 infection. The number of TNF+ and HHV-7+ lymphocytes, as well as HHV-7+ vascular endothelial cells, was strongly correlated. Vascular endothelial cells, especially in the case of infection reactivation, appeared vulnerable. The balance between virus latency and reactivation is a long-term relationship between the host and infectious agent, and the immune system appears to be involved in displaying overreaction when a shift in the established equilibrium develops.
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    Integrating Articular Cartilage Histopathology with CTX-II and COMP as Synovial Fluid Biomarkers for a Comprehensive Analysis in Osteoarthritis Evaluation
    (2024) Semenistaja, Sofija; Sokolovska, Lība; Studers, Pēteris; Kadiša, Anda; Groma, Valērija; Skuja, Sandra; Department of Doctoral Studies; Institute of Microbiology and Virology; Joint Laboratory of Traumatology and Orthopaedics; Department of Internal Diseases; Joint Laboratory of Electron Microscopy; Institute of Anatomy and Anthropology
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    Integrating Articular Cartilage Histopathology with CTX-II and COMP as Synovial Fluid Biomarkers for a Comprehensive Analysis in Osteoarthritis Evaluation
    (2024) Semenistaja, Sofija; Sokolovska, Lība; Studers, Pēteris; Kadiša, Anda; Groma, Valērija; Skuja, Sandra; Rīga Stradiņš University; Institute of Microbiology and Virology; Joint Laboratory of Traumatology and Orthopaedics; Department of Internal Diseases; Institute of Anatomy and Anthropology
    Osteoarthritis (OA) is the most common form of chronic joint disease characterized by the loss of cartilage as the primary site of the lesion. Both collagenous and non-collagenous proteins of the extracellular matrix (ECM) are dysregulated by the cellular component damage. Alterations in cartilage composition may manifest through variations in synovial fluid concentrations of C-terminal cross-linked telopeptides of type II collagen (CTX-II) and cartilage oligomeric matrix protein (COMP). This study seeks to decode histological alterations in the cartilage and establish a symbiotic relationship with concentrations of specific ECM proteins within the synovial fluid as potential OA biomarkers. Twenty-five surgically obtained cartilage tissue samples were stained with toluidine blue and analysed using the OARSI grading system under a light microscope both quantitatively and semi-quantitatively. The presence of CTX-II and COMP proteins was measured in the synovial fluid samples using ELISA. The SPSS 28.0 program was used for statistical data analysis. The OARSI score median value was 4.0 (3.0;4.5), attributable to the delamination of the superficial cartilage zone. A greater number of single cells in comparison with cellular clusters was found: 60.00 (45.00;84.00) and 26.00 (22.00;48.00), respectively. Proteoglycan staining was 1.00 (1.00;2.00), attributable to low intensity. A negative correlation between ECM oedema and proteoglycan staining was found (r = −0.445; p = 0.043). The mean levels of CTX-II and COMP in synovial fluid were 1092 pg/mL (SD 537.95) and 1262 ng/mL (SD 339.47), respectively. There was a positive correlation between CTX-II and OA severity (r = 0.305; p = 0.041); the COMP and OA severity correlation was negative (r = −0.286; p = 0.049). The identified positive correlation between OA severity and CTX-II levels in synovial fluid suggests that CTX-II may hold promise as a valuable biomarker for tracking OA progression. This implication opens up possibilities for early detection and targeted interventions in the management of the disease.
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    Osteoarthritis – the entire joint disease
    (2023) Groma, Valērija; Skuja, Sandra; Tarasovs, Mihails; Svirskis, Šimons; Semenistaja, Sofija; Rīga Stradiņš University
    Pertinent literature suggests that osteoarthritis (OA) emanates from the dysfunction of the whole joint, affecting the articular cartilage, synovium, and subchondral bone, the tissues revealing anatomical and molecular interactions. The study aimed to explore a spectrum of the structural joint damage characteristic of OA employing morphology methods. The entire joint tissues collected from 54 OA subjects (mean age 69 (range 35–85 years)) who underwent joint replacement surgery were processed and used in the study. Toluidine blue, Safranin O/Fast green, and Sirius red staining were used to detect proteoglycans, glycosaminoglycans, and collagen content of the articular cartilage. Synovitis was assessed using CD45, CD14, and CD68 (macrophages), CD45, and CD19 (B lymphocytes), CD45, CD3, CD4 (T lymphocytes), tumor necrosis factor alpha (TNF-α). Synovial fibroblasts were characterized by the expression of CD31, CD34, podoplanin (PDPN), and α-smooth muscle actin (α-SMA). Synovial histopathology was evaluated according to Krenn and Morawietz scores. Statistical data analysis and plotting were performed using Prism 9 and JMP Pro 16 software. Degradation of cartilage and changes in the proteoglycan and collagen content were confirmed using histochemical markers. Hypertrophic chondrocytes with abundant cytoplasmic inclusions, deep vascular invasions into the cartilage matrix, and reactive chondroclasts were evident. A median synovitis score was 2 (IQR 1–4). The synovial lesions consistent with low-grade synovitis demonstrated an increase in thickness of the lining layer (CD45/CD14/CD68 and CD31/CD34/PDPN positivity) and stromal cellularity (with CD68/ TNF-α positivity), the presence of a few, mostly perivascular CD45+/ CD3+/CD4+ lymphocytes. Loss of articular cartilage structure and function, and its remodeling is one of the major hallmarks of OA. Apart from the cartilage damage, synovial low-grade inflammation over time, or through injury, sustained during the life course has a strong cumulative impact and contributes to progressive OA-associated joint de struction.
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    Synovitis in osteoarthritic patients : Morphological and virological evidence of its contribution to development of the disease
    (2019-08-01) Tarasovs, Mihails; Skuja, Sandra; Semenistaja, Sofija; Murovska, Modra; Groma, Valerija; Institute of Anatomy and Anthropology; Department of Internal Diseases; Institute of Microbiology and Virology
    The role of inflammation in the development of osteoarthritic joint degeneration is not completely understood. Recent data suggest that processes that cause and orchestrate inflamed synovial lesions may be implicated in the development of the disease. The morphological changes of the synovium in patients with osteoarthritis (OA), as well as the level of synovial inflammation cautiously graded, in association to the presence of human parvovirus B19 (B19V) infection markers, were evaluated. Qualitative and quantitative detection of B19V genomic sequence was performed in OA and rheumatoid arthritis (RA) groups. The expression of CD68, S100 (Ca2+ binding proteins soluble in 100% ammonium sulfate) and B19 VP1/VP2 capsid proteins found in the synovium were investigated by single and double immunolabeling, whereas fine features of synoviocytes - by electron microscopy. One-third of OA and RA patients demonstrated synovial expression of B19V antigen, which was confirmed in both types of synoviocytes. The overall expression of B19V in OA patients was weaker than that found in RA subjects. Positive correlation between B19V-positive vascular endothelial cells, sublining infiltrating lymphocytes, macrophages, and B19V-positive synoviocytes was established. No correlation between synovitis score indices as well as the expression of S100 and expression of B19V was found. The results suggest that the synovial membrane maintains local joint homeostasis, and that virus mediated synovitis is implicated in the development of OA.
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    Synovitis in Osteoarthritic Patients: Morphological and Virological Evidence of its Contribution to Development of the Disease
    (2019) Tarasovs, Mihails; Skuja, Sandra; Semenistaja, Sofija; Murovska, Modra; Groma, Valērija
    The role of inflammation in the development of osteoarthritic joint degeneration is not completely understood. Recent data suggest that processes that cause and orchestrate inflamed synovial lesions may be implicated in the development of the disease. The morphological changes of the synovium in patients with osteoarthritis (OA), as well as the level of synovial inflammation cautiously graded, in association to the presence of human parvovirus B19 (B19V) infection markers, were evaluated. Qualitative and quantitative detection of B19V genomic sequence was performed in OA and rheumatoid arthritis (RA) groups. The expression of CD68, S100 (Ca2+ binding proteins soluble in 100% ammonium sulfate) and B19 VP1/VP2 capsid proteins found in the synovium were investigated by single and double immunolabeling, whereas fine features of synoviocytes — by electron microscopy. One-third of OA and RA patients demonstrated synovial expression of B19V antigen, which was confirmed in both types of synoviocytes. The overall expression of B19V in OA patients was weaker than that found in RA subjects. Positive correlation between B19V-positive vascular endothelial cells, sublining infiltrating lymphocytes, macrophages, and B19V-positive synoviocytes was established. No correlation between synovitis score indices as well as the expression of S100 and expression of B19V was found. The results suggest that the synovial membrane maintains local joint homeostasis, and that virus mediated synovitis is implicated in the development of OA.