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Lubricin
Proteoglycan 4 or lubricin is a proteoglycan that in humans is encoded by the ''PRG4'' gene. It acts as a joint/boundary lubricant. Function Lubricin is present in synovial fluid and on the surface (superficial layer) of articular cartilage and therefore plays an important role in joint lubrication and synovial homeostasis. When first isolated, cartilage lubricin was called "superficial zone protein" (SZP). Due to the discovery that the 32-kDa amino terminal fragment of lubricin could stimulate in-vitro megakaryocyte growth, the gene responsible for the expression of lubricin was initially called "megakaryocyte-stimulating factor" (MSF). However, Lubricin, MSF, and SZP are now collectively known as Proteoglycan 4 (hence PRG4 for the gene nomenclature). The evidence that lubricin is actually a proteoglycan is not solid. The expression of lubricin has also been detected and the protein localized in tendon, meniscus, lung, liver, heart, bone, ligament, muscle, and skin. It is pr ...
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Lubricin Lubricating Function
Proteoglycan 4 or lubricin is a proteoglycan that in humans is encoded by the ''PRG4'' gene. It acts as a joint/boundary lubricant. Function Lubricin is present in synovial fluid and on the surface (superficial layer) of articular cartilage and therefore plays an important role in joint lubrication and synovial homeostasis. When first isolated, cartilage lubricin was called "superficial zone protein" (SZP). Due to the discovery that the 32-kDa amino terminal fragment of lubricin could stimulate in-vitro megakaryocyte growth, the gene responsible for the expression of lubricin was initially called "megakaryocyte-stimulating factor" (MSF). However, Lubricin, MSF, and SZP are now collectively known as Proteoglycan 4 (hence PRG4 for the gene nomenclature). The evidence that lubricin is actually a proteoglycan is not solid. The expression of lubricin has also been detected and the protein localized in tendon, meniscus, lung, liver, heart, bone, ligament, muscle, and skin. It is pr ...
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Synovial Fluid
Synovial fluid, also called synovia, elp 1/sup> 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. Structure The inner membrane of synovial joints is called the synovial membrane and secretes synovial fluid into the joint cavity. Synovial fluid is an ultrafiltrate from plasma, and contains proteins derived from the blood plasma and proteins that are produced by cells within the joint tissues. The fluid contains hyaluronan secreted by fibroblast-like cells in the synovial membrane, lubricin (proteoglycan 4; PRG4) secreted by the surface chondrocytes of the articular cartilage and interstitial fluid filtered from the blood plasma. This fluid forms a thin layer (roughly 50 μm) at the surface of c ...
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Synovial Membrane
The synovial membrane (also known as the synovial stratum, synovium or stratum synoviale) 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 (type A) 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. Structure The synovial membrane is variable but often has two layers: * The outer layer, or subintima, can be of almost any type of connective tissue – fibrous (dense collagenous type), adipose (fatty; e.g. in intra-articular fat pads) or areolar (loose collagenous typ ...
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Cartilage
Cartilage is a resilient and smooth type of connective tissue. In tetrapods, it covers and protects the ends of long bones at the joints as articular cartilage, and is a structural component of many body parts including the rib cage, the neck and the bronchial tubes, and the intervertebral discs. In other taxa, such as chondrichthyans, but also in cyclostomes, it may constitute a much greater proportion of the skeleton. It is not as hard and rigid as bone, but it is much stiffer and much less flexible than muscle. The matrix of cartilage is made up of glycosaminoglycans, proteoglycans, collagen fibers and, sometimes, elastin. Because of its rigidity, cartilage often serves the purpose of holding tubes open in the body. Examples include the rings of the trachea, such as the cricoid cartilage and carina. Cartilage is composed of specialized cells called chondrocytes that produce a large amount of collagenous extracellular matrix, abundant ground substance that is rich in pro ...
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Vitronectin
Vitronectin (VTN or VN) is a glycoprotein of the hemopexin family which is abundantly found in serum, the extracellular matrix and bone. In humans it is encoded by the ''VTN'' gene. Vitronectin binds to integrin alpha-V beta-3 and thus promotes cell adhesion and spreading. It also inhibits the membrane-damaging effect of the terminal cytolytic complement pathway and binds to several serpins (serine protease inhibitors). It is a secreted protein and exists in either a single chain form or a clipped, two chain form held together by a disulfide bond. Vitronectin has been speculated to be involved in hemostasis and tumor malignancy. Structure Vitronectin is a 54 kDa glycoprotein, consisting of 478 amino acid residues. About one-third of the protein's molecular mass is composed of carbohydrates. On occasion, the protein is cleaved after arginine 379, to produce two-chain vitronectin, where the two parts are linked by a disulfide bond. No high-resolution structure has been determine ...
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Mucin
Mucins () are a family of high molecular weight, heavily glycosylated proteins (glycoconjugates) produced by epithelial tissues in most animals. Mucins' key characteristic is their ability to form gels; therefore they are a key component in most gel-like secretions, serving functions from lubrication to cell signalling to forming chemical barriers. They often take an inhibitory role. Some mucins are associated with controlling mineralization, including nacre formation in mollusks, calcification in echinoderms and bone formation in vertebrates. They bind to pathogens as part of the immune system. Overexpression of the mucin proteins, especially MUC1, is associated with many types of cancer. Although some mucins are membrane-bound due to the presence of a hydrophobic membrane-spanning domain that favors retention in the plasma membrane, most mucins are secreted as principal components of mucus by mucous membranes or are secreted to become a component of saliva. Genes Human muci ...
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Cell Adhesion
Cell adhesion is the process by which cells interact and attach to neighbouring cells through specialised molecules of the cell surface. This process can occur either through direct contact between cell surfaces such as cell junctions or indirect interaction, where cells attach to surrounding extracellular matrix, a gel-like structure containing molecules released by cells into spaces between them. Cells adhesion occurs from the interactions between cell-adhesion molecules (CAMs), transmembrane proteins located on the cell surface. Cell adhesion links cells in different ways and can be involved in signal transduction for cells to detect and respond to changes in the surroundings. Other cellular processes regulated by cell adhesion include cell migration and tissue development in multicellular organisms. Alterations in cell adhesion can disrupt important cellular processes and lead to a variety of diseases, including cancer and arthritis. Cell adhesion is also essential for in ...
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Chondrocyte
Chondrocytes (, from Greek χόνδρος, ''chondros'' = cartilage + κύτος, ''kytos'' = cell) are the only cells found in healthy cartilage. They produce and maintain the cartilaginous matrix, which consists mainly of collagen and proteoglycans. Although the word ''chondroblast'' is commonly used to describe an immature chondrocyte, the term is imprecise, since the progenitor of chondrocytes (which are mesenchymal stem cells) can differentiate into various cell types, including osteoblasts. Development From least- to terminally-differentiated, the chondrocytic lineage is: # Colony-forming unit-fibroblast # Mesenchymal stem cell / marrow stromal cell # Chondrocyte # Hypertrophic chondrocyte Mesenchymal (mesoderm origin) stem cells are undifferentiated, meaning they can differentiate into a variety of generative cells commonly known as osteochondrogenic (or osteogenic, chondrogenic, osteoprogenitor, etc.) cells. When referring to bone, or in this case cartilage, the origin ...
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Articular Cartilage
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. Structure Hyaline cartilage is covered externally by a fibrous membrane known as the perichondrium or, when it's along articulating surfaces, the synovial membrane. This membrane contains vessels that provide the cartilage with nutrition through diffusion. Hyaline cartilage matrix is primarily made of type II collagen and chondroitin sulphate, both of which are also found in elastic cartilage. Hyaline cartilage exists on the sternal ends of the ribs, in the larynx, trachea, and bronchi, and on the articulating surfaces of bones. It gives the structures a definite but pliable form. The presence of collagen fibres makes ...
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Proteoglycan
Proteoglycans are proteins that are heavily glycosylated. The basic proteoglycan unit consists of a "core protein" with one or more covalently attached glycosaminoglycan (GAG) chain(s). The point of attachment is a serine (Ser) residue to which the glycosaminoglycan is joined through a tetrasaccharide bridge (e.g. chondroitin sulfate- GlcA- Gal-Gal- Xyl-PROTEIN). The Ser residue is generally in the sequence -Ser-Gly-X-Gly- (where X can be any amino acid residue but proline), although not every protein with this sequence has an attached glycosaminoglycan. The chains are long, linear carbohydrate polymers that are negatively charged under physiological conditions due to the occurrence of sulfate and uronic acid groups. Proteoglycans occur in connective tissue. Types Proteoglycans are categorized by their relative size (large and small) and the nature of their glycosaminoglycan chains. Types include: Certain members are considered members of the "small leucine-rich proteoglyc ...
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Heparin
Heparin, also known as unfractionated heparin (UFH), is a medication and naturally occurring glycosaminoglycan. Since heparins depend on the activity of antithrombin, they are considered anticoagulants. Specifically it is also used in the treatment of heart attacks and unstable angina. It is given intravenously or by injection under the skin. Other uses for its anticoagulant properties include inside blood specimen test tubes and kidney dialysis machines. Common side effects include bleeding, pain at the injection site, and low blood platelets. Serious side effects include heparin-induced thrombocytopenia. Greater care is needed in those with poor kidney function. Heparin is contraindicated for suspected cases of vaccine-induced pro-thrombotic immune thrombocytopenia (VIPIT) secondary to SARS-CoV-2 vaccination, as heparin may further increase the risk of bleeding in an anti-PF4/heparin complex autoimmune manner, in favor of alternative anticoagulant medications (such as arg ...
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Hemopexin
Hemopexin (or haemopexin; Hpx; Hx), also known as beta-1B-glycoprotein, is a glycoprotein that in humans is encoded by the ''HPX'' gene and belongs to the hemopexin family of proteins. Hemopexin is the plasma protein with the highest binding affinity for heme. Hemoglobin ''itself'' circulating ''alone'' in the blood plasma (called ''free hemoglobin'', as opposed to the hemoglobin situated in and circulating with the red blood cell.) will soon be oxidized into met-hemoglobin which then further disassociates into ''free'' heme along with globin chain. The free heme will then be oxidized into free met-heme and sooner or later the hemopexin will come to bind free met-heme together, forming a complex of met-heme and hemopexin, continuing their journey in the circulation until reaching a receptor, such as CD91, on hepatocytes or macrophages within the spleen, liver and bone marrow. Hemopexin's arrival and subsequent binding to the free heme not only prevent heme's pro-oxidant and pr ...
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