Healthy and Osteoarthritis-Affected Joints Facing the Cellular Crosstalk

Funding Information: This study was supported by Rīga Stradiņš University Internal Research Grant Nr. 6-ZD-22/3/2022 “Identification of specific osteoarthritis phenotypes and disease endotypes tackled using the molecular and cellular assessment of the synovium-cartilage-bone interplay by correlation-based network analysis”. The article processing charge was covered by Rīga Stradiņš University Research Department. Publisher Copyright: © 2023 by the authors.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.publishersversionPeer reviewe

Synovitis in osteoarthritic patients : Morphological and virological evidence of its contribution to development of the disease

Funding Information: This study was supported by the National Research Programme Biomedicine for the Public Health (BIOMEDICINE), project 7.2 and the Latvian Council of Science, project [Interdisciplinary study of inflammatory joint disease-associated influence on neurocognitive function], project No. lzp-2018/1-0149. Finally, the authors would like to thank the Roche Academy for providing the study reagents. Publisher Copyright: © 2019 Mihails Tarasovs et al., published by Sciendo 2019. Copyright: Copyright 2019 Elsevier B.V., All rights reserved.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.Peer reviewe

Inflammatory Cytokine-Producing Cells and Inflammation Markers in the Synovium of Osteoarthritis Patients Evidenced in Human Herpesvirus 7 Infection

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

Synovitis in Osteoarthritic Patients: Morphological and Virological Evidence of its Contribution to Development of the Disease

MedicīnaVeselības aprūpeMedicineHealth CareIekaisuma nozīme locītavu deģenerācijas attīstībā osteoartrīta (OA) gadījumā nav pilnībā izzināta. Jaunākie dati liecina, ka procesi, kas veicina iekaisuma izraisītus bojājumus sinoviālās membrānas audos, var būt saistīti ar slimības attīstību. Pētījumā tika analizētas morfoloģiskās izmaiņas sinoviālās membrānas audos OA un reimatoīdā artrīta (RA) pacientiem, kā arī izvērtēta to korelācija ar imūnhistoķīmiski noteiktu cilvēka parvovīrusa B19 (B19V) antigēnu klātbūtni sinoviālo audu paraugos. CD68, S100 un B19 VP1/VP2 antigēnu imūnekspresija sinovija audos tika pētīta, izmantojot rutīnas un dubultās iezīmēšanas imūnhistoķīmijas metodes. OA (28.2%) un RA (28.6%) pacientiem tika novērota B19V antigēnu ekspresija sinoviālajā membrānā. Pētījumā tika novērota pozitīva korelācija starp B19V pozitīvajām endoteliālajām šūnām un sinoviālās membrānas stromālās daļas B19V pozitīvajiem limfocītiem, makrofāgiem, kā arī sinoviocītiem. Korelācija starp sinoviālo audu iekaisuma pakāpi un S100 ekspresiju, kā arī starp B19V ekspresiju un iekaisuma pakāpi netika atrasta. Pētījuma rezultāti liecina, ka sinoviālā membrāna uztur locītavas homeostāzi, un B19V infekcijas izraisīts sinoviālo audu iekaisums ir saistīts ar artrīta attīstību.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

Healthy and Osteoarthritis-Affected Joints Facing the Cellular Crosstalk

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