Light microscopic characterization of the fibroblast‐like synovial intimal cell (synoviocyte)

Wilkinson, Leonora; Pitsillides, Andrew A.; Worrall, J. G.; Edwards, J. C. W.

doi:10.1002/art.1780351010

Cited by 124 publications

(84 citation statements)

References 17 publications

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“…In previous studies, macrophage distribution has mainly been detailed using markers for CD14 and HLA-D molecules (24,(35)(36)(37)(38). For this study, markers of activated/mature macrophages were chosen: EBMl 1 , which recognizes CD68, an antigen expressed primarily within lysosomes in tissue macrophages and monocytes but which may also be weakly expressed by type B synoviocytes in the lining layer (39,40); RFD7, which recognizes mature tissue macrophages (41); and Ber-MAC3, which recognizes activated monocytes and tissue macrophages (42). Synovial expression of Ber-MAC3 has not previously been described, but some authors have used macrophage markers comparable with EBMl 1 and RFD7 (33,43,44).…”

Section: Discussionmentioning

confidence: 99%

Synovial tissue macrophage populations and articular damage in rheumatoid arthritis

Mulherin

FitzGerald

Bresnihan

1996

Arthritis & Rheumatism

453

310

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Objective. To examine the relative contribution of individual synovial cell populations to polyarticular destruction in rheumatoid arthritis (RA).Methods. Serial measurements of disease activity and articular destruction, obtained prospectively in 28 RA patients followed up for a mean of 5.8 years, were correlated with synovial cell populations quantified using immunohistochemical techniques.ResuZts. The mean radiologic score worsened (from 37 to 86; P = 0.OOOl) despite significant improvement in disease activity. Synovial lining layer cell depth and sublining layer macrophage, but not lymphocyte, cell counts correlated significantly with radiologic course. Detailed analysis of 11 patients demonstrated reduced synovial lining expression of CD14 compared with CD68 (P = 0.003), whereas sublining expression of CD14 and CD68 was equivalent. Conclusion. Synovial macrophage numbers correlated with articular destruction in RA. In addition, the study results provided further evidence that lining layer macrophages may represent a distinct subpopulation that is of importance in this process. These findings have implications for the development of new therapies for RA.Rheumatoid arthritis (RA) is characterized by synovial membrane inflammation leading to chronic polyarticular destruction (1,2). Increased lining layer cell depth is prominent, primarily as a result of accumulation of type A macrophage-derived lining cells, with some local proliferation of type B fibroblastDr. Mulherin

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Section: Discussionmentioning

confidence: 99%

Synovial tissue macrophage populations and articular damage in rheumatoid arthritis

Mulherin

FitzGerald

Bresnihan

1996

Arthritis & Rheumatism

453

310

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“…[12][13][14] In addition, increased levels of the principal HAreceptor, namely CD44, and local increases in HA availability in the extracellular matrix of the synovium's intimal surface, suggest that an increased synthesis and binding of HA by fibroblast-like synovial lining cells is one of the specialized characteristics of these cells in normal mature joints. 10,12,15,16 Furthermore, the finding that a single corticosteroid injection into RA joints both elevates synovial fluid HA concentrations toward those found in normal joints and diminishes disease-associated increases in serum HA concentrations, suggests that a restoration in both the HA synthetic capacity of the synovial lining as well as its barrier function for HA entry into the circulation is associated with the steroid-induced resurgence in joint function. 15,17 In order to determine the factors that exert a selective control over synoviocyte differentiation we have examined the initial appearance of these cells during embryonic development.…”

Section: Selective Ha Synthetic Ha-binding Characteristics In Joint mentioning

confidence: 99%

Identifying and characterizing the joint cavity‐forming cell

Pitsillides

2003

Cell Biochemistry & Function

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For many years, a large body of circumstantial evidence supported the notion that the synovial membrane produced the hyaluronan-rich synovial fluid. A quantitative cytochemical technique for uridine-diphospho glucose dehydrogenase (UDPGD) activity established that fibroblast-like cells on the intimal surface of the synovial lining made a specific contribution to maintaining these glycosaminoglycan levels. Our studies have aimed to determine the mechanisms that control the attainment and persistence of this differentiated phenotype, and have recently focused on their appearance during joint cavity development in the embryonic limb; a process that is dependent upon skeletal movement. These in situ micro-biochemical studies have shown that cells bordering the presumptive joint cavity exhibit raised UDPGD activity, are associated with a matrix rich in hyaluronan and show immobilization-induced loss in such characteristics. Together with complimentary studies in adult joints, this suggests that mechanical stimuli promote the acquisition of this joint line-forming phenotype. For this reason our studies have attempted to identify the 'up-stream' mechano-dependent factors that control these events. Endothelial cells respond to mechanical stimuli by activating, via phosphorylation, mitogen activated protein kinase/extracellular signal-regulated kinase (MAPkinase/ERK). Using phospho-specific anti-ERK-1/2 antibodies we have shown that immunolabelling of developing limbs shows a clear joint line-selective activation during cavitation, with little if any labelling within neighbouring elements, and that this is abolished in immobilized limbs. In an attempt to facilitate the final mechanistic deciphering of these responses we have used an in vitro-based approach and found by Western blotting that active ERK-1/2 expression was increased in cultured articular surface cells following application of dynamic mechanical strain. Intriguingly, the use of a selective inhibitor (PD98059) of ERK activation by its classical activating kinase, Mek, to restrict such strain-induced increases, produced an enhanced strain-related increase in UDPGD mRNA expression. This suggests that mechano-dependent ERK activation serves a feedback regulatory role during differentiation of these cells. Whilst it is clear that these in vitro experiments serve a useful function, it is clear that they generally take little regard of the influence that might be provided by cell-cell and cell-matrix interactions within the developing limb's complex and dynamic environment and architecture. It is therefore imperative that we attempt to bridge the gap between the cell biology of such phenomena on the one hand, and the morphological approach to this same problem on the other.

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“…There is evidence of at least two, and likely three joint capsular synoviocytes in a number of species; type A, type B, and a transitional or stem cell-like cell (type C). 10,17,18 Small heat shock proteins play an important role in cellular defense and HSP25 is upregulated in response to injury. 29,30 With light and TEM, HSP25 was localized to the cytoplasm and the nucleus consistent with previous study findings.…”

Section: Discussionmentioning

confidence: 99%

“…[10][11][12][13][14][15][16][17][18] The synoviocyte phenotypes identified include the type A (macrophage-like), type B (fibroblast-like), and an intermediate type (type C). [10][11][12][13][14][15][16][17][18] To date, techniques used to characterize joint capsular synoviocytes have not been applied to ACL-associated synoviocytes. Expression of cathepsin K and tartrate resistant acid phosphatase (TRAP), both collagenolytic enzymes, are elevated in ruptured canine ACLs and in joint capsular synovium from humans with rheumatoid arthritis.…”

mentioning

confidence: 99%

Characterization of normal canine anterior cruciate ligament–associated synoviocytes

Vasanjee

Paulsen

Hosgood

et al. 2008

Journal Orthopaedic Research

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This study was designed to identify and quantify synoviocyte phenotypes enveloping the canine anterior cruciate ligament (ACL) to test the hypothesis that there are at least two synoviocyte phenotypes, each with distinct quantities and topographical distributions. CD18 and HSP25 epitopes were colocalized in the synovium of 10 normal canine ACLs. Sagittal sections were prepared from medial, central, and lateral aspects of each ACL and phenotypes were quantified in the proximal, middle, and distal aspects of each section. Distinct synoviocyte populations stained positive for CD18 (CD18þ) or HSP25 (HSP25þ), and a small population of cells stained for both epitopes (DSþ). The proportion (mean AE SEM) of HSP25þ synoviocytes (57% AE 7.5%) was significantly greater than the proportion of CD18þ synoviocytes (27% AE 8.2%), which was significantly greater than the proportion of DSþ synoviocytes (16% AE 3.5%). Reverse transcriptase polymerase chain reaction (RT-PCR), Western blot analysis, and immunoelectron microscopy confirmed the presence of CD18 and HSP25 epitopes in the canine ACL. Identification and quantification of ACL synoviocytes may serve as the foundation for future studies involving ACL disease or reconstruction. ß

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Light microscopic characterization of the fibroblast‐like synovial intimal cell (synoviocyte)

Cited by 124 publications

References 17 publications

Synovial tissue macrophage populations and articular damage in rheumatoid arthritis

Synovial tissue macrophage populations and articular damage in rheumatoid arthritis

Identifying and characterizing the joint cavity‐forming cell

Characterization of normal canine anterior cruciate ligament–associated synoviocytes

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