PROPERTIES OF SYNOVIAL CELLS IN CULTURE

1971 ◽  
Vol 134 (3) ◽  
pp. 306-312 ◽  
Author(s):  
Carol A. Smith
Keyword(s):  
Rheumatoid Arthritis ◽  
Human Fibroblasts ◽  
Viral Persistence ◽  
Synovial Cells ◽  
Synovial Lining ◽  
Cellular Changes ◽  
Synovial Lining Cells ◽  
Synovial Membranes ◽  
And Cartilage

Derangements of synovial membranes and cartilage occur early in the course of rheumatoid arthritis. These important alterations of the joint tissues are probably the in vivo reflections of complicated inflammatory and immunological events. In our laboratory we have been interested in studying alterations of synovial lining cells in rheumatoid arthritis, most recently by the use of serially propagated cultures of these cells. The cellular traits described in such cultures serve to distinguish these synovial cells from other types of human fibroblasts, and several cellular alterations have been found in cultures derived from membranes of rheumatoid arthritic patients. One important finding is increased resistance of cultured rheumatoid cells to infection with rubella and NDV; this and other cellular changes suggest the possibility of an occult virus infection in the rheumatoid cells. Such viral persistence could be theoretically linked with the immunologic aberrations in rheumatoid arthritis, discussed in this symposium.

scholarly journals Hexokinase 2 as a novel selective metabolic target for rheumatoid arthritis

2018 ◽  
Vol 77 (11) ◽  
pp. 1636-1643 ◽  
Author(s):  
Marta F Bustamante ◽  
Patricia G Oliveira ◽  
Ricard Garcia-Carbonell ◽  
Adam P Croft ◽  
Jeff M Smith ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Glucose Metabolism ◽  
Cartilage Damage ◽  
Critical Role ◽  
Lactate Production ◽  
Migration And Invasion ◽  
Synovial Lining ◽  
Serum Transfer ◽  
And Cartilage

ObjectivesRecent studies indicate that glucose metabolism is altered in rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS). Hexokinases (HKs) catalyse the first step in glucose metabolism, and HK2 constitutes the principal HK inducible isoform. We hypothesise that HK2 contributes to the synovial lining hypertrophy and plays a critical role in bone and cartilage damage.MethodsHK1 and HK2 expression were determined in RA and osteoarthritis (OA) synovial tissue by immunohistochemistry. RA FLS were transfected with either HK1 or HK2 siRNA, or infected with either adenovirus (ad)-GFP, ad-HK1 or ad-HK2. FLS migration and invasion were assessed. To study the role of HK2 in vivo, 108 particles of ad-HK2 or ad-GFP were injected into the knee of wild-type mice. K/BxN serum transfer arthritis was induced in HK2F/F mice harbouring Col1a1-Cre (HK2Col1), to delete HK2 in non-haematopoietic cells.ResultsHK2 is particular of RA histopathology (9/9 RA; 1/8 OA) and colocalises with FLS markers. Silencing HK2 in RA FLS resulted in a less invasive and migratory phenotype. Consistently, overexpression of HK2 resulted in an increased ability to migrate and invade. It also increased extracellular lactate production. Intra-articular injection of ad-HK2 in normal knees dramatically increased synovial lining thickness, FLS activation and proliferation. HK2 was highly expressed in the synovial lining after K/BxN serum transfer arthritis. HK2Col1 mice significantly showed decreased arthritis severity, bone and cartilage damage.ConclusionHK2 is specifically expressed in RA synovial lining and regulates FLS aggressive functions. HK2 might be an attractive selective metabolic target safer than global glycolysis for RA treatment.

scholarly journals Biologically active thrombomodulin is synthesized by adherent synovial fluid cells and is elevated in synovial fluid of patients with rheumatoid arthritis

Blood ◽  
1993 ◽  
Vol 81 (3) ◽  
pp. 726-733 ◽  
Author(s):  
EM Conway ◽  
B Nowakowski
Keyword(s):  
Rheumatoid Arthritis ◽  
Synovial Fluid ◽  
Protein C ◽  
Inflammatory Process ◽  
Biologically Active ◽  
Northern Analysis ◽  
Synovial Lining ◽  
Local Synthesis ◽  
Synovial Lining Cells ◽  
Synovial Fluid Cells

Abstract Thrombomodulin (TM) is a transmembrane glycoprotein that interacts with thrombin, thereby serving as a cofactor in the activation of protein C, a major physiologically relevant natural anticoagulant. Although initially described as a vascular endothelial cell receptor, TM has also been reported to be synthesized by several cells, including megakaryocytes, platelets, monocytes, neutrophils (PMN), mesothelial cells, and synovial lining cells. A prominent feature of rheumatoid arthritis (RA) is infiltration of PMN into the joint space. To determine whether TM might play a role in the inflammatory process, we examined synovial fluid for the presence of TM in 10 patients with RA and five patients with osteoarthritis (OA). We determined that the mean synovial fluid and plasma TM levels in the OA group were 23.5 ng/mL and 24.2 ng/mL, respectively, whereas those with RA had a significantly elevated mean synovial fluid TM level of 136.2 ng/mL as compared with the plasma TM concentration of 43.9 ng/mL (P < .05). Synovial fluid TM levels did not correlate with PMN counts (r = .261). Purified TM from synovial fluid was identical in molecular weight to plasma-derived TM and was biologically functional with respect to protein C cofactor activity. Using direct immunofluorescence, we determined that adherent cultured synovial fluid cells that are not monocytoid in origin express surface and cytoplasmic TM, thereby providing an alternative source of the protein. Biologic activity of the cell-surface TM was confirmed by acceleration of thrombin-dependent protein C activation. Northern analysis of RNA extracted from the cultured cells indicated that TM messenger RNA was present, suggesting local synthesis. Our results indicate that in RA-associated synovial effusions, biologically active TM is increased, the source of which may be from plasma, PMN, and/or synovial lining cells. TM may play a regulatory role either in fibrin deposition in the inflamed joint and/or in the progression of the inflammatory process.

scholarly journals Studies of isolated synovial lining cells of rheumatoid and nonrheumatoid synovial membranes

1970 ◽  
Vol 13 (6) ◽  
pp. 734-753 ◽  
Author(s):  
T. Douglas Kinsella ◽  
John Baum ◽  
Morris Ziff
Keyword(s):  
Synovial Lining ◽  
Synovial Lining Cells ◽  
Synovial Membranes

The Third Dimension of Rheumatoid Arthritis

1970 ◽  
Vol 28 ◽  
pp. 338-339
Author(s):  
Jeanne M. Riddle ◽  
Gilbert B. Bluhm
Keyword(s):  
Rheumatoid Arthritis ◽  
Electron Microscopy ◽  
Membrane Surface ◽  
Three Dimensional ◽  
Joint Space ◽  
Cell Contact ◽  
Synovial Lining ◽  
Synovial Lining Cells ◽  
Third Dimension ◽  
Dynamic Quality

Our application of scanning electron microscopy to the investigation of synovial membrane surface topography in humans has yielded new morphologic information. Samples of synovium removed from patients with advanced rheumatoid arthritis exhibited projecting villi such as those depicted in Fig. 1 as a prominent feature of their three-dimensional microarchi-tecture. In addition, localized areas of fibrin deposition, large parallel folds and focal irregular cavities were observed. Synovial lining cells were protuberant, increased in number and variable in size with many larger synoviocytes evident. Individual synoviocytes or small clusters were separated by only narrow areas of intercellular matrix. Membrane activities such as erythrophagocytosis and pinocytosis, the latter illustrated in Fig. 2, attested to the dynamic quality of the synovial lining cells as they participated in this inflammatory disease state. Frequently individual synovial lining cells were connected by slender, intercellular cytoplasmic spans. This form of cellular linkage illustrated in Fig. 2-was heretofore undiscovered by studies utilizing either light or transmission electron microscopy. Large finger-like structures depicted in Fig. 2 also jutted from some synoviocytes and either extended into the joint space or bridged gaps between adjacent synovial lining cells. In the latter situation, these filopodia perhaps served as a second type of adhesive cell contact as the layers of synoviocytes increased in depth.

Molecular Lysis of Synovial Lining Cells by In Vivo Herpes Simplex Virus-Thymidine Kinase Gene Transfer

1998 ◽  
Vol 9 (18) ◽  
pp. 2735-2743 ◽  
Author(s):  
Susan M. Sant ◽  
Therese M. Suarez ◽  
Maria R. Moalli ◽  
Bei-Yue Wu ◽  
Mila Blaivas ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Gene Transfer ◽  
Thymidine Kinase ◽  
Thymidine Kinase Gene ◽  
Synovial Lining ◽  
Kinase Gene ◽  
Synovial Lining Cells ◽  
Simplex Virus
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