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Acta Clinica Croatica Dec 2019Bone endures a lifelong course of construction and destruction, with bone marker (BM) molecules released during this cycle. The field of measuring BM levels in synovial... (Review)
Review
Bone endures a lifelong course of construction and destruction, with bone marker (BM) molecules released during this cycle. The field of measuring BM levels in synovial fluid and peripheral blood is a cardinal part of bone research within modern clinical medicine and has developed extensively in the last years. The purpose of our work was to convey an up-to-date overview on synovial fluid and serum BMs in the most common arthropathies.
Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Female; Humans; Joint Diseases; Male; Middle Aged; Synovial Fluid
PubMed: 32595257
DOI: 10.20471/acc.2019.58.04.19 -
International Journal of Molecular... Oct 2022The quality of the lubricant between cartilaginous joint surfaces impacts the joint's mechanistic properties. In this study, we define the biochemical, ultrastructural,...
The quality of the lubricant between cartilaginous joint surfaces impacts the joint's mechanistic properties. In this study, we define the biochemical, ultrastructural, and tribological signatures of synovial fluids (SF) from patients with degenerative (osteoarthritis-OA) or inflammatory (rheumatoid arthritis-RA) joint pathologies in comparison with SF from healthy subjects. Phospholipid (PL) concentration in SF increased in pathological contexts, but the proportion PL relative to the overall lipids decreased. Subtle changes in PL chain composition were attributed to the inflammatory state. Transmission electron microscopy showed the occurrence of large multilamellar synovial extracellular vesicles (EV) filled with glycoprotein gel in healthy subjects. Synovial extracellular vesicle structure was altered in SF from OA and RA patients. RA samples systematically showed lower viscosity than healthy samples under a hydrodynamic lubricating regimen whereas OA samples showed higher viscosity. In turn, under a boundary regimen, cartilage surfaces in both pathological situations showed high wear and friction coefficients. Thus, we found a difference in the biochemical, tribological, and ultrastructural properties of synovial fluid in healthy people and patients with osteoarthritis and arthritis of the joints, and that large, multilamellar vesicles are essential for good boundary lubrication by ensuring a ball-bearing effect and limiting the destruction of lipid layers at the cartilage surface.
Topics: Cartilage, Articular; Extracellular Vesicles; Glycoproteins; Humans; Lubricants; Osteoarthritis; Phospholipids; Synovial Fluid
PubMed: 36233300
DOI: 10.3390/ijms231911998 -
Journal of Orthopaedic Research :... Aug 2020The objectives of this study were to evaluate temporal changes in lubricin, hyaluronan (HA), and HA molecular weight (MW) distributions in three distinct models of... (Comparative Study)
Comparative Study
The objectives of this study were to evaluate temporal changes in lubricin, hyaluronan (HA), and HA molecular weight (MW) distributions in three distinct models of equine joint injury affecting the carpal (wrist), tarsal (ankle), and femoropatellar (knee) joints. To establish ranges for lubricin, HA, and HA MW distributions across multiple joints, we first evaluated clinically healthy, high-motion equine joints. Synovial fluid was collected from high-motion joints in horses without clinical signs of joint disease (n = 11 horses, 102 joints) and from research horses undergoing carpal osteochondral fragmentation (n = 8), talar cartilage impact injury (n = 7), and femoral trochlear ridge full-thickness cartilage injury (n = 22) prior to and following arthroscopically induced joint injury. Lubricin and HA concentrations were measured via enzyme-linked immunosorbent assays, and gel electrophoresis was performed to evaluate HA MW distributions. Synovial fluid parameters were analyzed via linear regression models, revealing that lubricin and HA concentrations were conserved across healthy, high-motion joints. Lubricin concentrations increased post-injury in all osteoarthritis models (carpal fragmentation P = .001; talar impact P < .001; femoral trochlear ridge cartilage defect P = .03). Sustained loss of HA was noted post-arthroscopy following carpal osteochondral fragmentation (P < .0001) and talar impact injury (P < .001). Lubricin may be elevated to compensate for the loss of HA and to protect cartilage post-injury. Further investigation into the mechanisms regulating lubricin and HA following joint injury and their effects on joint homeostasis is warranted, including whether lubricin has value as a biomarker for post-traumatic osteoarthritis.
Topics: Animals; Female; Glycoproteins; Horses; Hyaluronic Acid; Joint Diseases; Joints; Male; Synovial Fluid
PubMed: 31965593
DOI: 10.1002/jor.24597 -
Osteoarthritis and Cartilage Jan 2023Since the joint microenvironment and tissue homeostasis are highly dependent on synovial fluid, we aimed to compare the essential chondrocyte signaling signatures of...
OBJECTIVE
Since the joint microenvironment and tissue homeostasis are highly dependent on synovial fluid, we aimed to compare the essential chondrocyte signaling signatures of non-osteoarthritic vs end-stage osteoarthritic knee synovial fluid. Moreover, we determined the phenotypic consequence of the distinct signaling patterns on articular chondrocytes.
METHODS
Protein profiling of synovial fluid was performed using antibody arrays. Chondrocyte signaling and phenotypic changes induced by non-osteoarthritic and osteoarthritic synovial fluid were analyzed using a phospho-kinase array, luciferase-based transcription factor activity assays, and RT-qPCR. The origin of osteoarthritic synovial fluid signaling was evaluated by comparing the signaling responses of conditioned media from cartilage, synovium, infrapatellar fat pad and meniscus. Osteoarthritic synovial fluid induced pathway-phenotype relationships were evaluated using pharmacological inhibitors.
RESULTS
Compared to non-osteoarthritic synovial fluid, osteoarthritic synovial fluid was enriched in cytokines, chemokines and growth factors that provoked differential MAPK, AKT, NFκB and cell cycle signaling in chondrocytes. Functional pathway analysis confirmed increased activity of these signaling events upon osteoarthritic synovial fluid stimulation. Tissue secretomes of osteoarthritic cartilage, synovium, infrapatellar fat pad and meniscus activated several inflammatory signaling routes. Furthermore, the distinct pathway signatures of osteoarthritic synovial fluid led to accelerated chondrocyte dedifferentiation via MAPK/ERK signaling, increased chondrocyte fibrosis through MAPK/JNK and PIK/AKT activation, an elevated inflammatory response mediated by cPKC/NFκB, production of extracellular matrix-degrading enzymes by MAPK/p38 and PIK/AKT routes, and enabling of chondrocyte proliferation.
CONCLUSION
This study provides the first mechanistic comparison between non-osteoarthritic and osteoarthritic synovial fluid, highlighting MAPKs, cPKC/NFκB and PIK/AKT as crucial OA-associated intracellular signaling routes.
Topics: Chondrocytes; Synovial Fluid; Cartilage, Articular; Proto-Oncogene Proteins c-akt; Cells, Cultured; Phenotype
PubMed: 36150677
DOI: 10.1016/j.joca.2022.09.004 -
The Veterinary Clinics of North... Jan 2017Synovial fluid analysis is a key component of the minimum database needed to diagnose and manage primary and secondary articular joint disorders. Unfortunately,... (Review)
Review
Synovial fluid analysis is a key component of the minimum database needed to diagnose and manage primary and secondary articular joint disorders. Unfortunately, preanalytical variables can drastically alter samples submitted for evaluation to veterinary laboratories and it is considered the stage at which most laboratory error occurs. This article addresses common sources of preanalytical variability and error that are seen in veterinary medicine. With consistent quality control and reporting of specimens, downstream clinical decision making and management of patients can be accelerated and improved.
Topics: Animals; Cytological Techniques; Specimen Handling; Synovial Fluid
PubMed: 27720280
DOI: 10.1016/j.cvsm.2016.07.007 -
Stem Cell Research & Therapy Oct 2014Mesenchymal stem cells (MSCs) have the ability to differentiate into osteoblasts, chondroblasts, adipocytes, and even myoblasts. Most studies have focused on finding... (Review)
Review
Mesenchymal stem cells (MSCs) have the ability to differentiate into osteoblasts, chondroblasts, adipocytes, and even myoblasts. Most studies have focused on finding MSCs in different parts of the body for medical treatment. Every joint structure, including bone, joint fat, articular cartilage, and synovium, potentially contains resident MSCs. Recently, a progenitor cell population has been found in synovial fluid and showed similarities with both bone marrow and synovial membrane MSCs. Synovial fluid MSCs have been studied in healthy persons and osteoarthritic patients in order to explore its potential for treatment of some orthopedic disorders. Here, we briefly review the current knowledge on synovial fluid MSCs, their origin, relation to some orthopedic diseases, and future applications.
Topics: Cell Differentiation; Cells, Cultured; Humans; Mesenchymal Stem Cells; Synovial Fluid; Synovial Membrane
PubMed: 25688673
DOI: 10.1186/scrt501 -
Journal of Orthopaedic Research :... Dec 2022Osteoarthritis occurs frequently after joint injury. Currently, osteoarthritis is diagnosed by radiographic changes that are typically found after the disease has...
Osteoarthritis occurs frequently after joint injury. Currently, osteoarthritis is diagnosed by radiographic changes that are typically found after the disease has progressed to multiple tissues. The primary objective was to compare potential metabolomic biomarkers of joint injury between synovial fluid and serum in a mouse model of posttraumatic osteoarthritis. The secondary objective was to gain insight into the pathophysiology of osteoarthritis by examining metabolomic profiles after joint injury. Twelve-week-old adult female C57BL/6 mice (n = 12) were randomly assigned to control, Day 1, or Day 8 postinjury groups. Randomly selected stifle joints were subjected to a single rapid compression. At Days 1 and 8 postinjury, serum was extracted before mice were euthanized for synovial fluid collection. Metabolomic profiling detected ~2500 metabolites across serum and synovial fluid. Of these, 179 were positively correlated and 51 were negatively correlated between synovial fluid and serum, indicating the potential for the development of metabolomic biomarkers. Synovial fluid captured injury-induced differences in metabolomic profiles at both Days 1 and 8 after injury whereas serum did not. However, synovial fluid and serum were distinct at both time points after injury. In synovial fluid, pathways of interest mapped to amino acid synthesis and degradation, bupropion degradation, and transfer RNA (tRNA) charging. In serum, pathways were amino acid synthesis and degradation, the phospholipase pathway, and nicotine degradation. These results provide a rich picture of the injury response at early time points after joint injury. Furthermore, the correlations between synovial fluid and serum metabolites suggest the potential to gain insight into intra-articular pathophysiology through analysis of serum metabolites.
Topics: Animals; Female; Mice; Amino Acids; Biomarkers; Joint Diseases; Mice, Inbred C57BL; Osteoarthritis; Synovial Fluid
PubMed: 35285551
DOI: 10.1002/jor.25310 -
Clinical Immunology (Orlando, Fla.) Dec 2023Synovial fluid (SF) extracellular vesicles (EVs) play a pathogenic role in osteoarthritis (OA). However, the surface markers, cell and tissue origins, and effectors of...
Synovial fluid (SF) extracellular vesicles (EVs) play a pathogenic role in osteoarthritis (OA). However, the surface markers, cell and tissue origins, and effectors of these EVs are largely unknown. We found that SF EVs contained 692 peptides that were positively associated with knee radiographic OA severity; 57.4% of these pathogenic peptides were from 46 proteins of the immune system, predominantly the innate immune system. CSPG4, BGN, NRP1, and CD109 are the major surface markers of pathogenic SF EVs. Genes encoding surface marker CSPG4 and CD109 were highly expressed by chondrocytes from damaged cartilage, while VISG4, MARCO, CD163 and NRP1 were enriched in the synovial immune cells. The frequency of CSPG4 and VSIG4 EV subpopulations in OA SF was high. We conclude that pathogenic SF EVs carry knee OA severity-associated proteins and specific surface markers, which could be developed as a new source of diagnostic biomarkers or therapeutic targets in OA.
Topics: Humans; Osteoarthritis, Knee; Synovial Fluid; Biomarkers; Peptides; Extracellular Vesicles
PubMed: 37866785
DOI: 10.1016/j.clim.2023.109812 -
Annals of the Rheumatic Diseases Jun 1991High performance liquid chromatography with TSK 5000 PW or TSK 6000 PW size exclusion columns combined with a 125I labelled hyaluronic acid binding protein assay was...
High performance liquid chromatography with TSK 5000 PW or TSK 6000 PW size exclusion columns combined with a 125I labelled hyaluronic acid binding protein assay was used to study the effects of oxygen derived free radicals on synovial fluid hyaluronate. A continuous flux of free radicals was generated by the xanthine oxidase/hypoxanthine system. When the free radical flux was generated with xanthine oxidase/hypoxanthine in the presence of the iron chelator desferrioxamine and the hydroxyl radical scavenger mannitol a 30-50% decrease in hyaluronate peak was detected, but the molecular weight of synovial fluid hyaluronate remained almost unchanged as a result of reaction with superoxide radicals and hydrogen peroxide. When trace amounts of iron and EDTA were present in the reaction mixture depolymerisation of synovial fluid hyaluronate occurred, and it reached a final molecular weight of about 13,500 daltons. These results suggest that superoxide and hydroxyl radicals may have a different mode of action on synovial fluid hyaluronate. Superoxide radicals and hydrogen peroxide do not induce depolymerisation but, rather, change the molecular configuration of synovial fluid hyaluronate.
Topics: Carrier Proteins; Chromatography, High Pressure Liquid; Free Radicals; Humans; Hyaluronan Receptors; Hyaluronic Acid; Oxygen; Synovial Fluid
PubMed: 1711835
DOI: 10.1136/ard.50.6.389 -
Osteoarthritis and Cartilage Jun 2022Alterations in the composition of synovial fluid have been associated with adverse effects on cartilage integrity and function. Here, we examined the phenotypic and...
OBJECTIVES
Alterations in the composition of synovial fluid have been associated with adverse effects on cartilage integrity and function. Here, we examined the phenotypic and proliferative behavior of human articular chondrocytes when cultured in vitro for 13 days with synovial fluid derived from end-stage osteoarthritis patients.
MATERIALS AND METHODS
Chondrocyte proliferation and phenotypical changes induced by osteoarthritic synovial fluid were analyzed using DNA staining, RT-qPCR, immunostainings, and immunoblotting. The molecular mechanisms by which osteoarthritic synovial fluid induced fibrosis and proliferation were studied using a phospho-protein antibody array and luciferase-based transcription factor activity assays. Specific pathway inhibitors were used to probe the involvement of pathways in fibrosis and proliferation.
RESULTS
Prolonged stimulation with osteoarthritic synovial fluid sustained chondrocyte proliferation and induced profound phenotypic changes, favoring a fibrotic over a chondrogenic or hypertrophic phenotype. A clear loss of chondrogenic markers at both the transcriptional and protein level was observed, while expression of several fibrosis-associated markers were upregulated over time. Phospho-kinase analysis revealed activation of MAPK and RhoGTPase signaling pathways by osteoarthritic synovial fluid, which was confirmed by elevated transcriptional activity of Elk-1 and SRF. Inhibitor studies revealed that ERK played a central role in the loss of chondrocyte phenotype, while EGFR and downstream mediators p38, JNK and Rac/Cdc42 were essential for fibrosis-associated collagen expression. Finally, we identified EGF signaling as a key activator of chondrocyte proliferation.
CONCLUSIONS
Osteoarthritic synovial fluid promoted chondrocyte fibrosis and proliferation through EGF receptor activation and downstream MAPK and RhoGTPase signaling.
Topics: Cartilage, Articular; Cell Proliferation; Cells, Cultured; Chondrocytes; Fibrosis; Humans; Osteoarthritis; Synovial Fluid
PubMed: 35176481
DOI: 10.1016/j.joca.2021.12.015