Fibroblast-like synoviocyte

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Fibroblast-like synoviocyte
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Location Synovium
Anatomical terms of microanatomy

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 inflammatory diseases, such as rheumatoid arthritis.

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Fibroblast-like synoviocytes in normal tissues

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 macrophages (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. [1] [2]

Fibroblast-like synoviocytes are cells of mesenchymal origin that display many characteristics common with fibroblasts, such as expression of several types of collagens and protein vimentin, a part of 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 integrins 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. [3]

The role of fibroblast-like synoviocytes in the pathogenesis of rheumatoid arthritis

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 inflammatory processes take place, which can eventually lead to cartilage damage and joint destruction and deformation. Due to the changes in proliferative and apoptotic processes the total number of cells increases in the synovium, and significantly increases also the number of fibroblast-like synoviocytes (FLS). These cells, together with other immune cells such as macrophages, lymphocytes, neutrophils, mast cells, dendritic cells and platelets, create an inflammatory environment in the synovium, attract more immune cells to the damaged place and thus contribute to the joint destruction. [1] [2] [3]

FLS that are present in the synovium during RA 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 FLS 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 Il-6 and IL-8, prostanoids and matrix metalloproteinases (MMPs), which may directly affect other cells and also participate in the inflammation enhancement. [3] These processes are influenced by microvesicles derived from platelets, which can contribute to the activation of fibroblast-like synoviocytes through secretion of IL-1. [4]

The aggressive phenotype of FLS in RA and the effect these cells have on their microenvironment can be summarized into hallmarks that distinguish them from healthy FLS. These hallmark features of FLS in RA are divided into 7 cell-intrinsic hallmarks and 4 cell-extrinsic hallmarks. [5] The cell-intrinsic hallmarks are: reduced apoptosis, impaired contact inhibition, increased migratory invasive potential, changed epigenetic landscape, temporal and spatial heterogeneity, genomic instability and mutations, and reprogrammed cellular metabolism. The cell-extrinsic hallmarks of FLS in RA are: promotes osteoclastogenesis and bone erosion, contributes to cartilage degradation, induces synovial angiogenesis, and recruits and stimulates immune cells. [5]

Related Research Articles

<span class="mw-page-title-main">Rheumatoid arthritis</span> Type of autoimmune arthritis

Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and hands are involved, with the same joints typically involved on both sides of the body. The disease may also affect other parts of the body, including skin, eyes, lungs, heart, nerves and blood. This may result in a low red blood cell count, inflammation around the lungs, and inflammation around the heart. Fever and low energy may also be present. Often, symptoms come on gradually over weeks to months.

<span class="mw-page-title-main">Synovial membrane</span> Connective tissue present within and around synovial joints

The synovial membrane is a specialized connective tissue that lines the inner surface of capsules of synovial joints and tendon sheath. It makes direct contact with the fibrous membrane on the outside surface and with the synovial fluid lubricant on the inside surface. In contact with the synovial fluid at the tissue surface are many rounded macrophage-like synovial cells and also type B cells, which are also known as fibroblast-like synoviocytes (FLS). Type A cells maintain the synovial fluid by removing wear-and-tear debris. As for the FLS, they produce hyaluronan, as well as other extracellular components in the synovial fluid.

<span class="mw-page-title-main">Synovial joint</span> Articulation which admits free motion in the joint; the most common type of articulation

A synovial joint, also known as diarthrosis, joins bones or cartilage with a fibrous joint capsule that is continuous with the periosteum of the joined bones, constitutes the outer boundary of a synovial cavity, and surrounds the bones' articulating surfaces. This joint unites long bones and permits free bone movement and greater mobility. The synovial cavity/joint is filled with synovial fluid. The joint capsule is made up of an outer layer of fibrous membrane, which keeps the bones together structurally, and an inner layer, the synovial membrane, which seals in the synovial fluid.

<span class="mw-page-title-main">Synovial fluid</span> Fluid found in the cavities of synovial joints

Synovial fluid, also called synovia,[help 1] is a viscous, non-Newtonian fluid found in the cavities of synovial joints. With its egg white–like consistency, the principal role of synovial fluid is to reduce friction between the articular cartilage of synovial joints during movement. Synovial fluid is a small component of the transcellular fluid component of extracellular fluid.

<span class="mw-page-title-main">Hyaline cartilage</span> Type of cartilage in animals

Hyaline cartilage is the glass-like (hyaline) and translucent cartilage found on many joint surfaces. It is also most commonly found in the ribs, nose, larynx, and trachea. Hyaline cartilage is pearl-gray in color, with a firm consistency and has a considerable amount of collagen. It contains no nerves or blood vessels, and its structure is relatively simple.

Pannus is an abnormal layer of fibrovascular tissue or granulation tissue. Common sites for pannus formation include over the cornea, over a joint surface, or on a prosthetic heart valve. Pannus may grow in a tumor-like fashion, as in joints where it may erode articular cartilage and bone.

Stromal cells, or mesenchymal stromal cells, are differentiating cells found in abundance within bone marrow but can also be seen all around the body. Stromal cells can become connective tissue cells of any organ, for example in the uterine mucosa (endometrium), prostate, bone marrow, lymph node and the ovary. They are cells that support the function of the parenchymal cells of that organ. The most common stromal cells include fibroblasts and pericytes. The term stromal comes from Latin stromat-, "bed covering", and Ancient Greek στρῶμα, strôma, "bed".

<span class="mw-page-title-main">Synovitis</span> Medical condition

Synovitis is the medical term for inflammation of the synovial membrane. This membrane lines joints that possess cavities, known as synovial joints. The condition is usually painful, particularly when the joint is moved. The joint usually swells due to synovial fluid collection.

Felty's syndrome (FS), also called Felty syndrome, is a rare autoimmune disease characterized by the triad of rheumatoid arthritis, enlargement of the spleen and low neutrophil count. The condition is more common in those aged 50–70 years, specifically more prevalent in females than males, and more so in Caucasians than those of African descent. It is a deforming disease that causes many complications for the individual.

<span class="mw-page-title-main">Interleukin 20</span> Protein-coding gene in the species Homo sapiens

Interleukin 20 (IL20) is a protein that is in humans encoded by the IL20 gene which is located in close proximity to the IL-10 gene on the 1q32 chromosome. IL-20 is a part of an IL-20 subfamily which is a part of a larger IL-10 family.

Synovectomy is a procedure where the synovial tissue surrounding a joint is removed. This procedure is typically recommended to provide relief from a condition in which the synovial membrane or the joint lining becomes inflamed and irritated and is not controlled by medication alone. If arthritis is not controlled, it can lead to irreversible joint damage. The synovial membrane or "synovium" encloses each joint and also secretes a lubricating fluid that allows different joint motions such as rolling, folding and stretching. When the synovium becomes inflamed or irritated, it increases fluid production, resulting in warmth, tenderness, and swelling in and around the joint.

Osteoimmunology is a field that emerged about 40 years ago that studies the interface between the skeletal system and the immune system, comprising the "osteo-immune system". Osteoimmunology also studies the shared components and mechanisms between the two systems in vertebrates, including ligands, receptors, signaling molecules and transcription factors. Over the past decade, osteoimmunology has been investigated clinically for the treatment of bone metastases, rheumatoid arthritis (RA), osteoporosis, osteopetrosis, and periodontitis. Studies in osteoimmunology reveal relationships between molecular communication among blood cells and structural pathologies in the body.

<span class="mw-page-title-main">YWHAH</span> Protein-coding gene in the species Homo sapiens

14-3-3 protein eta also referred to as 14-3-3η is a protein that in humans is encoded by the YWHAH gene.

<span class="mw-page-title-main">CHI3L1</span> Protein-coding gene in the species Homo sapiens

Chitinase-3-like protein 1 (CHI3L1), also known as YKL-40, is a secreted glycoprotein that is approximately 40kDa in size that in humans is encoded by the CHI3L1 gene. The name YKL-40 is derived from the three N-terminal amino acids present on the secreted form and its molecular mass. YKL-40 is expressed and secreted by various cell-types including macrophages, chondrocytes, fibroblast-like synovial cells, vascular smooth muscle cells, and hepatic stellate cells. The biological function of YKL-40 is unclear. It is not known to have a specific receptor. Its pattern of expression is associated with pathogenic processes related to inflammation, extracellular tissue remodeling, fibrosis and solid carcinomas and asthma.

<span class="mw-page-title-main">CDH11</span> Protein-coding gene in the species Homo sapiens

Cadherin-11 is a protein that in humans is encoded by the CDH11 gene.

<span class="mw-page-title-main">Proteoglycan 4</span> Proteoglycan; lubricant; gene

Proteoglycan 4 or lubricin is a proteoglycan that in humans is encoded by the PRG4 gene. It acts as a joint/boundary lubricant.

<span class="mw-page-title-main">Rheumatoid nodule</span> Medical condition

A rheumatoid nodule is a lump of tissue, or an area of swelling, that appears on the exterior of the skin usually around the olecranon or the interphalangeal joints, but can appear in other areas. There are four different types of rheumatoid nodules: subcutaneous rheumatoid nodules, cardiac nodules, pulmonary nodules, and central nervous systems nodules. These nodules occur almost exclusively in association with rheumatoid arthritis. Very rarely do rheumatoid nodules occur as rheumatoid nodulosis in the absence of rheumatoid arthritis. Rheumatoid nodules can also appear in areas of the body other than the skin. Less commonly they occur in the lining of the lungs or other internal organs. The occurrence of nodules in the lungs of miners exposed to silica dust was known as Caplan’s syndrome. Rarely, the nodules occur at diverse sites on body.

Gene therapy for osteoarthritis is the application of gene therapy to treat osteoarthritis (OA). Unlike pharmacological treatments which are administered locally or systemically as a series of interventions, gene therapy aims to establish sustained therapeutic effect after a single, local injection.

<span class="mw-page-title-main">Gary Firestein</span> American rheumatologist

Gary S. Firestein is an American rheumatologist, professor, and founding director of the Altman Clinical and Translational Research Institute (ACTRI) at the University of California San Diego and Senior Associate Vice Chancellor for Health Sciences at University of California, San Diego.

Radiosynoviorthesis (RSO) is a minimally invasive therapeutic procedure for managing joint inflammation, particularly synovitis associated with osteoarthritis. Radiosynoviorthesis involves the intra-articular injection of radioactive isotopes to specifically treat the inflamed synovial membrane. Synovitis, a hallmark of various joint disorders, including osteoarthritis, manifests as inflammation within the synovial membrane lining the joints. RSO aims to suppress overactive macrophage and synovial cells responsible for the inflammatory response, providing relief from pain and improving joint functionality.

References

  1. 1 2 Kyung Chang, Sook; Gu, Zhizhan; Brenner, Michael B. (2010). "Fibroblast-like synoviocytes in inflammatory arthritis pathology: The emerging role of cadherin-11". Immunological Reviews. 233 (1): 256–66. doi:10.1111/j.0105-2896.2009.00854.x. PMID   20193004. S2CID   9759438.
  2. 1 2 Dasuri, Kumar; Antonovici, Mihaela; Chen, Keding; Wong, Ken; Standing, Kenneth; Ens, Werner; El-Gabalawy, Hani; Wilkins, John A. (2004). "The synovial proteome: Analysis of fibroblast-like synoviocytes". Arthritis Research & Therapy . 6 (2): R161–8. doi: 10.1186/ar1153 . PMC   400437 . PMID   15059280.
  3. 1 2 3 Bartok, Beatrix; Firestein, Gary S. (2010). "Fibroblast-like synoviocytes: Key effector cells in rheumatoid arthritis". Immunological Reviews. 233 (1): 233–55. doi:10.1111/j.0105-2896.2009.00859.x. PMC   2913689 . PMID   20193003.
  4. ↑ Boilard, E.; Nigrovic, P. A.; Larabee, K.; Watts, G. F. M.; Coblyn, J. S.; Weinblatt, M. E.; Massarotti, E. M.; Remold-o'Donnell, E.; et al. (2010). "Platelets Amplify Inflammation in Arthritis via Collagen-Dependent Microparticle Production". Science. 327 (5965): 580–3. Bibcode:2010Sci...327..580B. doi:10.1126/science.1181928. PMC   2927861 . PMID   20110505.
  5. 1 2 Nygaard, G.; Firestein, G. S. (2020). "Restoring synovial homeostasis in rheumatoid arthritis by targeting fibroblast-like synoviocytes". Nature Reviews Rheumatology. 16 (6): 316–333. doi:10.1038/s41584-020-0413-5. PMC   7987137 . PMID   32393826.
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