Fibroblast-like synoviocyte: Difference between revisions

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{{Infobox cell
'''Fibroblast-like synoviocytes (FLS)''' are specialized cells found in the [[synovium]], the inner lining of joints, and play a pivotal role in the pathogenesis of chronic inflammatory diseases, such as [[rheumatoid arthritis]] (RA). These cells are important for maintaining the homeostasis of the joint, but their dysregulation can contribute to joint damage and disease progression.
| Name        = Fibroblast-like synoviocyte 
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| Location    = [[Synovium]]
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'''Fibroblast-like synoviocytes (FLS)''' represent a specialised cell type located inside joints in the [[synovium]]. These cells play a crucial role in the pathogenesis of chronic [[inflammation|inflammatory]] diseases, such as [[rheumatoid arthritis]].


== Fibroblast-like synoviocytes in normal tissues ==
==Fibroblast-like synoviocytes in Normal Tissues==
The synovium, also referred to as the [[synovial membrane]], is a thin layer of tissue that lines the joint cavity. It is situated between the [[joint capsule]] and the joint cavity, and its primary function is to produce [[synovial fluid]]. Synovial fluid, a clear, viscous liquid, lubricates the joints and reduces friction between the cartilages during movement. In addition to lubrication, the synovium provides structural support to the joint and delivers necessary nutrients to the surrounding [[cartilage]].


The inner lining of the joint consists of the synovium (also called the synovial membrane), a thin layer located between the joint capsule and the joint cavity. The word "synovium" is derived from the word "synovia" (or [[synovial fluid]]), which is a clear, viscous fluid produced by the synovium, and its main purpose is to reduce friction between the joint cartilages during movement. Synovium is also important to maintain proper joint function by providing the structural support and supply of the necessary nutrients to the surrounding cartilage. Synovial membrane is divided into two compartments the outer layer (subintima) and the inner layer (intima). The inner layer is mainly composed of two cell types, specialized [[macrophage]]s (macrophage-like synovial cells) and fibroblast-like synoviocytes, which are important in maintaining the internal joint [[homeostasis]]. These cells represent the main source of [[hyaluronic acid]] and also other glycoproteins, major components of the synovial fluid.<ref name=chang>{{cite journal |doi=10.1111/j.0105-2896.2009.00854.x |title=Fibroblast-like synoviocytes in inflammatory arthritis pathology: The emerging role of cadherin-11 |year=2010 |last1=Kyung Chang |first1=Sook |last2=Gu |first2=Zhizhan |last3=Brenner |first3=Michael B. |journal=Immunological Reviews |volume=233 |pages=256–66 |pmid=20193004 |issue=1}}</ref><ref name=dasuri>{{cite journal |doi=10.1186/ar1153 |year=2004 |last1=Dasuri |first1=Kumar |last2=Antonovici |first2=Mihaela |last3=Chen |first3=Keding |last4=Wong |first4=Ken |last5=Standing |first5=Kenneth |last6=Ens |first6=Werner |last7=El-Gabalawy |first7=Hani |last8=Wilkins |first8=John A |journal=[[Arthritis Research & Therapy]] |volume=6 |issue=2 |pmid=15059280 |pages=R161–8 |title=The synovial proteome: Analysis of fibroblast-like synoviocytes |pmc=400437}}</ref>
The synovial membrane is organized into two layers:
* '''Subintima''' The outer layer.
* '''Intima''' – The inner layer, which contains specialized cells that maintain joint function.


Fibroblast-like synoviocytes are cells of [[mesenchym]]al origin that display many characteristics common with [[fibroblast]]s, such as expression of several types of [[collagen]]s and protein [[vimentin]], a part of [[cytoskeleton|cytoskeletal]] filaments. Unlike fibroblasts, fibroblast-like synoviocytes also secrete unique proteins, that are normally absent in other fibroblast lineages. These include especially [[lubricin]], a protein crucial for the joint lubrication. Furthermore these cells express a number of molecules important for the mediation of the cell adhesion, such as [[cadherin-11]], [[VCAM-1]], various [[integrin]]s and their receptors. Specific for fibroblast-like synoviocytes is also the expression of [[CD55]]; this protein is often used to identify this cell type in the synovium by [[immunohistochemistry]].<ref name=bartok>{{cite journal |doi=10.1111/j.0105-2896.2009.00859.x |title=Fibroblast-like synoviocytes: Key effector cells in rheumatoid arthritis |year=2010 |last1=Bartok |first1=Beatrix |last2=Firestein |first2=Gary S. |journal=Immunological Reviews |volume=233 |pages=233–55 |pmid=20193003 |issue=1 |pmc=2913689}}</ref>
The inner layer of the synovium consists of two primary cell types: [[macrophage-like synovial cells]] and [[fibroblast-like synoviocytes]]. These cells are crucial for maintaining the internal environment of the joint. Fibroblast-like synoviocytes are responsible for the production of key components of the synovial fluid, such as [[hyaluronic acid]] and other [[glycoproteins]].


== The role of fibroblast-like synoviocytes in the pathogenesis of rheumatoid arthritis ==
Fibroblast-like synoviocytes are mesenchymal cells that share many characteristics with fibroblasts, such as the expression of various collagen types and [[vimentin]], a protein that is part of the cytoskeleton. However, these cells also produce unique proteins, such as [[lubricin]], which plays an essential role in joint lubrication. In addition, they express several molecules critical for cell adhesion, including [[cadherin-11]], [[VCAM-1]], and various [[integrins]] and their receptors. One distinctive feature of fibroblast-like synoviocytes is the expression of [[CD55]], a protein commonly used in immunohistochemistry to identify these cells in the synovium.


Synovial [[hyperplasia]] (an increase in cell number) is a typical feature of the autoimmune disease called [[rheumatoid arthritis]] (RA). During the progression of this disease the synovial membrane becomes a place where constant [[inflammation|inflammatory]] processes take place, which can eventually lead to cartilage damage and joint destruction and deformation. Due to the changes in [[Cell proliferation|proliferative]] and [[apoptose|apoptotic]] processes the total number of cells increases in the synovium, and significantly increases also the number of fibroblast-like synoviocytes. These cells, together with other immune cells such as [[macrophage]]s, [[lymphocyte]]s, [[neutrophil]]s, [[mast cell]]s, [[dendritic cell]]s and [[platelet]]s, create an inflammatory environment in the synovium, attract more immune cells to the damaged place and thus contribute to the joint destruction.<ref name=chang /><ref name=dasuri /><ref name=bartok />
==Role of Fibroblast-like Synoviocytes in Rheumatoid Arthritis==
Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation and synovial hyperplasia, where the number of synovial cells increases significantly. In RA, the synovium becomes the site of persistent inflammatory activity, leading to [[cartilage destruction]] and [[joint deformation]]. During disease progression, the number of fibroblast-like synoviocytes in the synovium increases, contributing to the inflammatory environment and subsequent joint damage.


Fibroblast-like synoviocytes that are present in the synovium during rheumatoid arthritis display altered [[phenotype]] compared to the cells present in normal tissues. They lose the property called [[contact inhibition]] (cells arrest their growth in the case when more cells come into contact with each other), and they also lose the growth dependency on adhesive surfaces; both these phenomena contribute to the increase in the number of fibroblast-like synoviocytes in the inflammatory tissue and are also typical for example for the growth of cancerous cells. In addition, these cells can produce a number of pro-inflammatory signalling molecules, especially [[interleukin 6|Il-6]] and [[interleukin 8|IL-8]], [[prostanoid]]s and [[matrix metalloproteinase]]s (MMPs), which may directly affect other cells and also participate in the inflammation enhancement.<ref name=bartok /> These processes are influenced by microvesicles derived from platelets, which can contribute to the activation of fibroblast-like synoviocytes through secretion of [[interleukin 1|IL-1]].<ref name=boilard>{{cite journal |doi=10.1126/science.1181928 |title=Platelets Amplify Inflammation in Arthritis via Collagen-Dependent Microparticle Production |year=2010 |last1=Boilard |first1=E. |last2=Nigrovic |first2=P. A. |last3=Larabee |first3=K. |last4=Watts |first4=G. F. M. |last5=Coblyn |first5=J. S. |last6=Weinblatt |first6=M. E. |last7=Massarotti |first7=E. M. |last8=Remold-o'Donnell |first8=E. |last9=Farndale |first9=R. W. |last10=Ware |first10=J. |last11=Lee |first11=D. M. |journal=Science |volume=327 |issue=5965 |pages=580–3 |pmid=20110505 |pmc=2927861|display-authors=8 }}</ref>
Fibroblast-like synoviocytes in RA display a distinct phenotype compared to those in normal tissues. In RA, these cells lose the phenomenon of [[contact inhibition]], a process in which cell growth is halted when cells come into contact with one another. Additionally, fibroblast-like synoviocytes in RA no longer depend on adhesive surfaces for growth, a characteristic that is also seen in cancer cells. These changes promote the unchecked proliferation of fibroblast-like synoviocytes in the inflamed synovium.


== References ==
Furthermore, these cells produce a variety of [[pro-inflammatory]] signaling molecules that exacerbate the inflammatory response. Key molecules include:
{{reflist}}
* [[Interleukin 6 (IL-6)]]
* [[Interleukin 8 (IL-8)]]
* [[Prostanoids]]
* [[Matrix metalloproteinases (MMPs)]]


[[Category:Immunology]]
These molecules can act on other cell types in the synovium and contribute to the amplification of the inflammatory cascade, ultimately leading to the destruction of cartilage and bone.
 
In addition to these factors, [[microvesicles]] derived from [[platelets]] can further activate fibroblast-like synoviocytes by releasing IL-1. This process underscores the complex interplay between various immune cells and fibroblast-like synoviocytes in the progression of RA.
 
==See Also==
* [[Rheumatoid arthritis]]
* [[Synovium]]
* [[Fibroblasts]]
* [[Cartilage destruction]]
* [[Interleukins]]
* [[Matrix metalloproteinases]]
{{stub}}
[[Category:Hematology]]
[[Category:Endocrinology]]
[[Category:Autoimmune diseases]]
[[Category:Joint diseases]]
[[Category:Rheumatology]]
[[Category:Rheumatology]]
{{dictionary-stub1}}

Latest revision as of 17:29, 1 April 2025

Fibroblast-like synoviocytes (FLS) are specialized cells found in the synovium, the inner lining of joints, and play a pivotal role in the pathogenesis of chronic inflammatory diseases, such as rheumatoid arthritis (RA). These cells are important for maintaining the homeostasis of the joint, but their dysregulation can contribute to joint damage and disease progression.

Fibroblast-like synoviocytes in Normal Tissues[edit]

The synovium, also referred to as the synovial membrane, is a thin layer of tissue that lines the joint cavity. It is situated between the joint capsule and the joint cavity, and its primary function is to produce synovial fluid. Synovial fluid, a clear, viscous liquid, lubricates the joints and reduces friction between the cartilages during movement. In addition to lubrication, the synovium provides structural support to the joint and delivers necessary nutrients to the surrounding cartilage.

The synovial membrane is organized into two layers:

  • Subintima – The outer layer.
  • Intima – The inner layer, which contains specialized cells that maintain joint function.

The inner layer of the synovium consists of two primary cell types: macrophage-like synovial cells and fibroblast-like synoviocytes. These cells are crucial for maintaining the internal environment of the joint. Fibroblast-like synoviocytes are responsible for the production of key components of the synovial fluid, such as hyaluronic acid and other glycoproteins.

Fibroblast-like synoviocytes are mesenchymal cells that share many characteristics with fibroblasts, such as the expression of various collagen types and vimentin, a protein that is part of the cytoskeleton. However, these cells also produce unique proteins, such as lubricin, which plays an essential role in joint lubrication. In addition, they express several molecules critical for cell adhesion, including cadherin-11, VCAM-1, and various integrins and their receptors. One distinctive feature of fibroblast-like synoviocytes is the expression of CD55, a protein commonly used in immunohistochemistry to identify these cells in the synovium.

Role of Fibroblast-like Synoviocytes in Rheumatoid Arthritis[edit]

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation and synovial hyperplasia, where the number of synovial cells increases significantly. In RA, the synovium becomes the site of persistent inflammatory activity, leading to cartilage destruction and joint deformation. During disease progression, the number of fibroblast-like synoviocytes in the synovium increases, contributing to the inflammatory environment and subsequent joint damage.

Fibroblast-like synoviocytes in RA display a distinct phenotype compared to those in normal tissues. In RA, these cells lose the phenomenon of contact inhibition, a process in which cell growth is halted when cells come into contact with one another. Additionally, fibroblast-like synoviocytes in RA no longer depend on adhesive surfaces for growth, a characteristic that is also seen in cancer cells. These changes promote the unchecked proliferation of fibroblast-like synoviocytes in the inflamed synovium.

Furthermore, these cells produce a variety of pro-inflammatory signaling molecules that exacerbate the inflammatory response. Key molecules include:

These molecules can act on other cell types in the synovium and contribute to the amplification of the inflammatory cascade, ultimately leading to the destruction of cartilage and bone.

In addition to these factors, microvesicles derived from platelets can further activate fibroblast-like synoviocytes by releasing IL-1. This process underscores the complex interplay between various immune cells and fibroblast-like synoviocytes in the progression of RA.

See Also[edit]

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