Collagen Type IX
Collagen
Cartilage
Collagen Type I
Collagen Type III
Collagen Type IV
Collagen Type II
Collagen Type XI
Collagen Type V
Fibrillar Collagens
Collagen Type VI
Extracellular Matrix
Extracellular Matrix Proteins
Receptors, Collagen
Chick Embryo
Pepsin A
Chondroitin Lyases
Cartilage, Articular
Collagen Type XVIII
Procollagen
Cells, Cultured
Collagen Type X
Matrilin Proteins
Collagen Type XII
Fibronectins
Hydroxyproline
COL9A3: A third locus for multiple epiphyseal dysplasia. (1/80)
Multiple epiphyseal dysplasia (MED), an autosomal dominant osteochondrodysplasia, is a clinically and genetically heterogeneous disorder characterized by mild short stature and early-onset osteoarthritis. The phenotypic spectrum includes the mild Ribbing type, the more severe Fairbank type, and some unclassified forms. Linkage studies have identified two loci for MED. One of these, EDM1, is on chromosome 19, in a region that contains the cartilage oligomeric matrix protein (COMP) gene. Mutations have been identified in this gene in patients with the Ribbing type, the Fairbank type, and unclassified forms of MED. The second locus, EDM2, maps to chromosome 1, in a region spanning COL9A2. Recently, a splice-site mutation was found in COL9A2, causing skipping of exon 3 in one family with MED. Because of the exclusion of the EDM1 and EDM2 loci in some families, the existence of a third locus has been postulated. We report here one family with MED, evaluated clinically and radiologically and tested for linkage with candidate genes, including COMP, COL9A1, COL9A2, and COL9A3. No linkage was found with COMP, COL9A1, or COL9A2, but an inheritance pattern consistent with linkage was observed with COL9A3. Mutation analysis of COL9A3 identified an A-->T transversion in the acceptor splice site of intron 2 in affected family members. The mutation led to skipping of exon 3 and an in-frame deletion of 12 amino acid residues in the COL3 domain of the alpha3(IX) chain and thus appeared to be similar to that reported for COL9A2. This is the first disease-causing mutation identified in COL9A3. Our results also show that COL9A3, located on chromosome 20, is a third locus for MED. (+info)An allele of COL9A2 associated with intervertebral disc disease. (2/80)
Intervertebral disc disease is one of the most common musculoskeletal disorders. A number of environmental and anthropometric risk factors may contribute to it, and recent reports have suggested the importance of genetic factors as well. The COL9A2 gene, which codes for one of the polypeptide chains of collagen IX that is expressed in the intervertebral disc, was screened for sequence variations in individuals with intervertebral disc disease. The analysis identified a putative disease-causing sequence variation that converted a codon for glutamine to one for tryptophan in six out of the 157 individuals but in none of 174 controls. The tryptophan allele cosegregated with the disease phenotype in the four families studied, giving a lod score (logarithm of odds ratio) for linkage of 4.5, and subsequent linkage disequilibrium analysis conditional on linkage gave an additional lod score of 7.1. (+info)Complete sequence of the 23-kilobase human COL9A3 gene. Detection of Gly-X-Y triplet deletions that represent neutral variants. (3/80)
We report the complete sequence of the human COL9A3 gene that encodes the alpha3 chain of heterotrimeric type IX collagen, a member of the fibril-associated collagens with interrupted triple helices family of collagenous proteins. Nucleotide sequencing defined over 23,000 base pairs (bp) of the gene and about 3000 bp of the 5'-flanking sequences. The gene contains 32 exons. The domain and exon organization of the gene is almost identical to a related gene, the human COL9A2 gene. However, exon 2 of the COL9A3 gene codes for one -Gly-X-Y- triplet less than exon 2 of the COL9A2 gene. The difference is compensated by an insertion of 9 bp coding for an additional triplet in exon 4 of the COL9A3 gene. As a result, the number of -Gly-X-Y- repeats in the third collagenous domain remains the same in both genes and ensures the formation of an in-register triple helix. In the course of screening this gene for mutations, heterozygosity for separate 9-bp deletions within the COL1 domain were identified in two kindreds. In both instances, the deletions did not co-segregate with any disease phenotype, suggesting that they were neutral variants. In contrast, similar deletions in triple helical domain of type I collagen are lethal. To study whether alpha3(IX) chains with the deletion will participate in the formation of correctly folded heterotrimeric type IX collagen, we expressed mutant alpha3 chains together with normal alpha1 and alpha2 chains in insect cells. We show here that despite the deletion, mutant alpha3 chains were secreted as heterotrimeric, triple helical molecules consisting of three alpha chains in a 1:1:1 ratio. The results suggest that the next noncollagenous domain (NC2) is capable of correcting the alignment of the alpha chains, and this ensures the formation of an in-register triple helix. (+info)A mutation in COL9A1 causes multiple epiphyseal dysplasia: further evidence for locus heterogeneity. (4/80)
Multiple epiphyseal dysplasia (MED) is an autosomal dominantly inherited chondrodysplasia. It is clinically highly heterogeneous, partially because of its complex genetic background. Mutations in four genes, COL9A2, COL9A3, COMP, and MATR3, all coding for cartilage extracellular matrix components (i.e., the alpha2 and alpha 3 chains of collagen IX, cartilage oligomeric matrix protein, and matrilin-3), have been identified in this disease so far, but no mutations have yet been reported in the third collagen IX gene, COL9A1, which codes for the alpha1(IX) chain. MED with apparently recessive inheritance has been reported in some families. A homozygous R279W mutation was recently found in the diastrophic dysplasia sulfate transporter gene, DTDST, in a patient with MED who had a club foot and double-layered patella. The series consisted of 41 probands with MED, 16 of whom were familial and on 4 of whom linkage analyses were performed. Recombination was observed between COL9A1, COL9A2, COL9A3, and COMP and the MED phenotype in two of the families, and between COL9A2, COL9A3, and COMP and the phenotype in the other two families. Screening of COL9A1 for mutations in the two probands from the families in which this gene was not involved in the recombinations failed to identify any disease-causing mutations. The remaining 37 probands were screened for mutations in all three collagen IX genes and in the COMP gene. The probands with talipes deformities or multipartite patella were also screened for the R279W mutation in DTDST. The analysis resulted in identification of three mutations in COMP and one in COL9A1, but none in the other two collagen IX genes. Two of the probands with a multipartite patella had the homozygous DTDST mutation. The results show that mutations in COL9A1 can cause MED, but they also suggest that mutations in COL9A1, COL9A2, COL9A3, COMP, and DTDST are not the major causes of MED and that there exists at least one additional locus. (+info)Chondrocyte phenotype and cell survival are regulated by culture conditions and by specific cytokines through the expression of Sox-9 transcription factor. (5/80)
OBJECTIVE: To investigate the effects of culture conditions, serum and specific cytokines such as insulin-like growth factor (IGF) 1 and interleukin (IL) 1alpha on phenotype and cell survival in cultures of Syrian hamster embryonic chondrocyte-like cells (DES4(+).2). METHODS: Proteins and RNA extracted from subconfluent and confluent early- and late-passage DES4(+).2 cells cultured in the presence or absence of serum and IL-1alpha or IGF-1 or both cytokines together were analysed for the expression of chondrocyte-specific genes and for the chondrogenic transcription factor Sox-9 by Western and Northern blotting. Apoptosis was assessed by agarose gel electrophoresis of labelled low-molecular weight DNA extracted from DES4(+).2 cells and another Syrian hamster embryonic chondrocyte-like cell line, 10W(+).1, cultured under the different conditions and treatments. RESULTS: Early passage DES4(+).2 cells expressed chondrocyte-specific molecules such as collagen types alpha1(II) and alpha1(IX), aggrecan, biglycan and link protein and collagen types alpha1(I) and alpha1(X) mRNAs, suggesting a prehypertrophic chondrocyte-like phenotype. The expression of all genes investigated was cell density- and serum-dependent and was low to undetectable in cell populations from later passages. Early-passage DES4(+).2 and 10W(+).1 cells survived when cultured at low cell density, but died by apoptosis when cultured at high cell density in the absence of serum or IGF-1. IGF-1 and IL-1alpha had opposite and antagonistic effects on the chondrocyte phenotype and survival. Whereas IL-1alpha acting alone suppressed cartilage-specific gene expression without significantly affecting cell survival, IGF-1 increased the steady-state mRNA levels and relieved the IL-1alpha-induced suppression of all the chondrocyte-specific genes investigated; it also enhanced chondrocyte survival. Suppression of the chondrocyte phenotype by the inflammatory cytokine IL-1alpha correlated with marked down-regulation of the transcription factor Sox-9, which was relieved by IGF-1. The expression of the Sox9 gene was closely correlated with the expression of the chondrocyte-specific genes under all conditions and treatments. CONCLUSIONS: The results suggest that the effects of cartilage anabolic and catabolic cytokines IGF-1 and IL-1alpha on the expression of the chondrocyte phenotype are mediated by Sox-9. As Sox-9 appears to be essential for matrix production, the potent effect of IL-1alpha in suppressing Sox-9 expression may limit the ability of cartilage to repair during inflammatory joint diseases. (+info)Contacts with fibrils containing collagen I, but not collagens II, IX, and XI, can destabilize the cartilage phenotype of chondrocytes. (6/80)
OBJECTIVE: Cell-matrix interactions are important regulators of cellular functions, including matrix synthesis, proliferation and differentiation. This is well exemplified by the characteristically labile phenotype of chondrocytes that is lost in monolayer culture but is stabilized in suspension under appropriate conditions. We were interested in the role of collagen suprastructures in maintaining or destabilizing the cartilage phenotype of chondrocytes. DESIGN: Primary sternal chondrocytes from 17-day-old chick embryos were cultured in gels of fibrils reconstituted from soluble collagen I from various sources. The culture media either contained or lacked FBS. Cells were cultured for up to 28 days and the evolution of the phenotype of the cells was assessed by their collagen expression (collagens II and X for differentiated chondrocytes and hypertrophic chodrocytes, repectively; collagen I for phenotypically modulated cells), or by their secretion of alkaline phosphatase (hypertrophic cartilage phenotype). RESULTS: The cells often retained their differentiated phenotype only if cultured with serum. Under serum-free conditions, cartilage characteristics were lost. The cells acquired a fibroblast-like shape and, later, synthesized collagen I instead of cartilage collagens. Shape changes were influenced by beta1-integrin-activity, whereas other matrix receptors were important for alterations of collagen patterns. Heterotypic fibrils reconstituted from collagens II, IX, and XI did not provoke this phenotypic instability. CONCLUSIONS: Chondrocytes sensitively recognize the suprastructures of collagen fibrils in their environment. Cellular interactions with fibrils with appropriate molecular organizations, such as that in cartilage fibrils, result in the maintenance of the differentiated cartilage phenotype. However, other suprastructures, e.g. in reconstituted fibrils mainly containing collagen I, lead to cell-matrix interactions incompatible with the cartilage phenotype. The maintenance of the differentiated traits of chondrocytes is pivotal for the normal function of, e.g., articular cartilage. If pathologically altered matrix suprastructures lead to a dysregulation of collagen production also in vivo compromised cartilage functions inevitably will be propagated further. (+info)Articular cartilage repair using a tissue-engineered cartilage-like implant: an animal study. (7/80)
OBJECTIVE: Because articular cartilage has limited ability to repair itself, treatment of (osteo)chondral lesions remains a clinical challenge. We aimed to evaluate how well a tissue-engineered cartilage-like implant, derived from chondrocytes cultured in a novel patented, scaffold-free bioreactor system, would perform in minipig knees with chondral, superficial osteochondral, and full-thickness articular defects. DESIGN: For in vitro implant preparation, we used full-thickness porcine articular cartilage and digested chondrocytes. Bioreactors were seeded with 20x10(6) cells and incubated for 3 weeks. Subsequent to culture, tissue cartilage-like implants were divided for assessment of viability, formaldehyde-fixed and processed by standard histological methods. Some samples were also prepared for electron microscopy (TEM). Proteoglycans and collagens were identified and quantified by SDS-PAGE gels. For in vivo studies in adult minipigs, medial parapatellar arthrotomy was performed unilaterally. Three types of defects were created mechanically in the patellar groove of the femoral condyle. Tissue-engineered cartilage-like implants were placed using press-fit fixation, without supplementary fixation devices. Control defects were not grafted. Animals could bear full weight with an unlimited range of motion. At 4 and 24 weeks postsurgery, explanted knees were assessed using the modified ICRS classification for cartilage repair. RESULTS: After 3-4 weeks of bioreactor incubation, cultured chondrocytes developed a 700-microm- to 1-mm-thick cartilage-like tissue. Cell density was similar to that of fetal cartilage, and cells stained strongly for Alcian blue and safranin O. The percentage of viable cells remained nearly constant (approximately 90%). Collagen content was similar to that of articular cartilage, as shown by SDS-PAGE. At explantation, the gross morphological appearance of grafted defects appeared like normal cartilage, whereas controls showed irregular fibrous tissue covering the defect. Improved histologic appearance was maintained for 6 months postoperatively. Although defects were not always perfectly level upon implantation at explanation the implant level matched native cartilage levels with no tissue hypertrophy. Once in place, implants remodelled to tissues with decreased cell density and a columnar organization. CONCLUSIONS: Repair of cartilage defects with a tissue-engineered implant yielded a consistent gross cartilage repair with a matrix predominantly composed of type II collagen up to 6 months after implantation. This initial result holds promise for the use of this unique bioreactor/tissue-engineered implant in humans. (+info)The chick transcriptional repressor Nkx3.2 acts downstream of Shh to promote BMP-dependent axial chondrogenesis. (8/80)
Previously, we demonstrated that Shh acts early in the development of the axial skeleton, to induce a prochondrogenic response to later BMP signaling. Here, we demonstrate that somitic expression of the transcription factor Nkx3.2 is initiated by Shh and sustained by BMP signals. Misexpression of Nkx3.2 in somitic tissue confers a prochondrogenic response to BMP signals. The transcriptional repressor activity of Nkx3.2 is essential for this factor to promote chondrogenesis. Conversely, a "reverse function" mutant of Nkx3.2 that has been converted into a transcriptional activator inhibits axial chondrogenesis in vivo. We conclude that Nkx3.2 is a critical mediator of the actions of Shh during axial cartilage formation, acting to inhibit expression of factors that interfere with the prochondrogenic effects of BMPs. (+info)Collagen type IX is a type of collagen that is found in the extracellular matrix, particularly in the cartilage and vitreous humor of the eye. It is a heterotrimeric protein made up of three alpha chains (alpha1, alpha2, and alpha3), which are encoded by different genes (COL9A1, COL9A2, and COL9A3). Collagen type IX is thought to play a role in the organization and stability of collagen fibrils, as well as in the interaction between collagen and other extracellular matrix components. It has been implicated in various connective tissue disorders, such as Stickler syndrome and Marshall syndrome.
Collagen is the most abundant protein in the human body, and it is a major component of connective tissues such as tendons, ligaments, skin, and bones. Collagen provides structure and strength to these tissues and helps them to withstand stretching and tension. It is made up of long chains of amino acids, primarily glycine, proline, and hydroxyproline, which are arranged in a triple helix structure. There are at least 16 different types of collagen found in the body, each with slightly different structures and functions. Collagen is important for maintaining the integrity and health of tissues throughout the body, and it has been studied for its potential therapeutic uses in various medical conditions.
Cartilage is a type of connective tissue that is found throughout the body in various forms. It is made up of specialized cells called chondrocytes, which are embedded in a firm, flexible matrix composed of collagen fibers and proteoglycans. This unique structure gives cartilage its characteristic properties of being both strong and flexible.
There are three main types of cartilage in the human body: hyaline cartilage, elastic cartilage, and fibrocartilage.
1. Hyaline cartilage is the most common type and is found in areas such as the articular surfaces of bones (where they meet to form joints), the nose, trachea, and larynx. It has a smooth, glassy appearance and provides a smooth, lubricated surface for joint movement.
2. Elastic cartilage contains more elastin fibers than hyaline cartilage, which gives it greater flexibility and resilience. It is found in structures such as the external ear and parts of the larynx and epiglottis.
3. Fibrocartilage has a higher proportion of collagen fibers and fewer chondrocytes than hyaline or elastic cartilage. It is found in areas that require high tensile strength, such as the intervertebral discs, menisci (found in joints like the knee), and the pubic symphysis.
Cartilage plays a crucial role in supporting and protecting various structures within the body, allowing for smooth movement and providing a cushion between bones to absorb shock and prevent wear and tear. However, cartilage has limited capacity for self-repair and regeneration, making damage or degeneration of cartilage tissue a significant concern in conditions such as osteoarthritis.
Collagen Type I is the most abundant form of collagen in the human body, found in various connective tissues such as tendons, ligaments, skin, and bones. It is a structural protein that provides strength and integrity to these tissues. Collagen Type I is composed of three alpha chains, two alpha-1(I) chains, and one alpha-2(I) chain, arranged in a triple helix structure. This type of collagen is often used in medical research and clinical applications, such as tissue engineering and regenerative medicine, due to its excellent mechanical properties and biocompatibility.
Collagen Type III, also known as Collagen III Alpha 1 (COL3A1), is a type of collagen that is found in various connective tissues throughout the body. It is a fibrillar collagen that is produced by fibroblasts and is a major component of reticular fibers, which provide structural support to organs such as the liver, spleen, and lymph nodes. Collagen Type III is also found in the walls of blood vessels, the skin, and the intestinal tract.
Mutations in the COL3A1 gene can lead to a rare genetic disorder called Ehlers-Danlos syndrome type IV, which is characterized by fragile and elastic skin, easy bruising, and spontaneous rupture of blood vessels. Collagen Type III has been studied for its potential role in various other medical conditions, including fibrosis, cancer, and cardiovascular disease.
Collagen Type IV is a type of collagen that forms the structural basis of basement membranes, which are thin, sheet-like structures that separate and support cells in many types of tissues. It is a major component of the basement membrane's extracellular matrix and provides strength and flexibility to this structure. Collagen Type IV is composed of three chains that form a distinctive, mesh-like structure. Mutations in the genes encoding Collagen Type IV can lead to a variety of inherited disorders affecting the kidneys, eyes, and ears.
Collagen Type II is a specific type of collagen that is a major component of the extracellular matrix in articular cartilage, which is the connective tissue that covers and protects the ends of bones in joints. It is also found in other tissues such as the vitreous humor of the eye and the inner ear.
Collagen Type II is a triple helix molecule composed of three polypeptide chains that contain a high proportion of the amino acids proline and hydroxyproline. This type of collagen provides structural support and elasticity to tissues, and it also plays a role in the regulation of cell behavior and signaling.
Collagen Type II is a target for autoimmune responses in conditions such as rheumatoid arthritis, where the immune system mistakenly attacks the body's own collagen, leading to joint inflammation and damage. It is also a common component of various dietary supplements and therapies used to support joint health and treat osteoarthritis.
Collagen type XI is a fibrillar collagen that is found in the extracellular matrix of various tissues, including cartilage and the eye. It is a homotrimer made up of three identical alpha 1(XI) chains or a heterotrimer composed of two alpha 1(XI) chains and one alpha 2(XI) chain. Collagen type XI is closely associated with collagen type II fibrils and plays a role in regulating the diameter and organization of these fibrils. Mutations in the genes encoding collagen type XI can lead to skeletal disorders such as stiff skin syndrome and fibrodysplasia ossificans progressiva.
Collagen Type V is a specific type of collagen, which is a protein that provides structure and strength to connective tissues in the body. Collagen Type V is found in various tissues, including the cornea, blood vessels, and hair. It plays a crucial role in the formation of collagen fibers and helps regulate the diameter of collagen fibrils. Mutations in the genes that encode for Collagen Type V can lead to various connective tissue disorders, such as Ehlers-Danlos syndrome and osteogenesis imperfecta.
Fibrillar collagens are a type of collagen that form rope-like fibrils in the extracellular matrix of connective tissues. They are composed of three polypeptide chains, called alpha chains, which are coiled together in a triple helix structure. The most common types of fibrillar collagens are Type I, II, III, V, and XI. These collagens provide strength and support to tissues such as tendons, ligaments, skin, and bones. They also play important roles in the regulation of cell behavior and tissue development. Mutations in genes encoding fibrillar collagens can lead to a variety of connective tissue disorders, including osteogenesis imperfecta, Ehlers-Danlos syndrome, and Marfan syndrome.
Collagen Type VI is a type of collagen that is widely expressed in various tissues, including skeletal muscle, skin, and blood vessels. It is a major component of the extracellular matrix and plays important roles in maintaining tissue structure and function. Collagen Type VI forms microfilaments that provide structural support to the basement membrane and regulate cell-matrix interactions. Mutations in the genes encoding collagen Type VI can lead to several inherited connective tissue disorders, such as Bethlem myopathy and Ullrich congenital muscular dystrophy.
The extracellular matrix (ECM) is a complex network of biomolecules that provides structural and biochemical support to cells in tissues and organs. It is composed of various proteins, glycoproteins, and polysaccharides, such as collagens, elastin, fibronectin, laminin, and proteoglycans. The ECM plays crucial roles in maintaining tissue architecture, regulating cell behavior, and facilitating communication between cells. It provides a scaffold for cell attachment, migration, and differentiation, and helps to maintain the structural integrity of tissues by resisting mechanical stresses. Additionally, the ECM contains various growth factors, cytokines, and chemokines that can influence cellular processes such as proliferation, survival, and differentiation. Overall, the extracellular matrix is essential for the normal functioning of tissues and organs, and its dysregulation can contribute to various pathological conditions, including fibrosis, cancer, and degenerative diseases.
Extracellular matrix (ECM) proteins are a group of structural and functional molecules that provide support, organization, and regulation to the cells in tissues and organs. The ECM is composed of a complex network of proteins, glycoproteins, and carbohydrates that are secreted by the cells and deposited outside of them.
ECM proteins can be classified into several categories based on their structure and function, including:
1. Collagens: These are the most abundant ECM proteins and provide strength and stability to tissues. They form fibrils that can withstand high tensile forces.
2. Proteoglycans: These are complex molecules made up of a core protein and one or more glycosaminoglycan (GAG) chains. The GAG chains attract water, making proteoglycans important for maintaining tissue hydration and resilience.
3. Elastin: This is an elastic protein that allows tissues to stretch and recoil, such as in the lungs and blood vessels.
4. Fibronectins: These are large glycoproteins that bind to cells and ECM components, providing adhesion, migration, and signaling functions.
5. Laminins: These are large proteins found in basement membranes, which provide structural support for epithelial and endothelial cells.
6. Tenascins: These are large glycoproteins that modulate cell adhesion and migration, and regulate ECM assembly and remodeling.
Together, these ECM proteins create a microenvironment that influences cell behavior, differentiation, and function. Dysregulation of ECM proteins has been implicated in various diseases, including fibrosis, cancer, and degenerative disorders.
Collagen receptors are a type of cell surface receptor that bind to collagen molecules, which are the most abundant proteins in the extracellular matrix (ECM) of connective tissues. These receptors play important roles in various biological processes, including cell adhesion, migration, differentiation, and survival.
Collagen receptors can be classified into two major groups: integrins and discoidin domain receptors (DDRs). Integrins are heterodimeric transmembrane proteins that consist of an alpha and a beta subunit. They bind to collagens via their arginine-glycine-aspartic acid (RGD) motif, which is located in the triple-helical domain of collagen molecules. Integrins mediate cell-collagen interactions by clustering and forming focal adhesions, which are large protein complexes that connect the ECM to the cytoskeleton.
DDRs are receptor tyrosine kinases (RTKs) that contain a discoidin domain in their extracellular region, which is responsible for collagen binding. DDRs bind to collagens via their non-RGD motifs and induce intracellular signaling pathways that regulate cell behavior.
Abnormalities in collagen receptor function have been implicated in various diseases, including fibrosis, cancer, and inflammation. Therefore, understanding the structure and function of collagen receptors is crucial for developing novel therapeutic strategies to treat these conditions.
A chick embryo refers to the developing organism that arises from a fertilized chicken egg. It is often used as a model system in biological research, particularly during the stages of development when many of its organs and systems are forming and can be easily observed and manipulated. The study of chick embryos has contributed significantly to our understanding of various aspects of developmental biology, including gastrulation, neurulation, organogenesis, and pattern formation. Researchers may use various techniques to observe and manipulate the chick embryo, such as surgical alterations, cell labeling, and exposure to drugs or other agents.
Pepsin A is defined as a digestive enzyme that is primarily secreted by the chief cells in the stomach's fundic glands. It plays a crucial role in protein catabolism, helping to break down food proteins into smaller peptides during the digestive process. Pepsin A has an optimal pH range of 1.5-2.5 for its enzymatic activity and is activated from its inactive precursor, pepsinogen, upon exposure to acidic conditions in the stomach.
Chondroitin lyases are a group of enzymes that breakdown chondroitin, which is a type of proteoglycan found in connective tissues such as cartilage. These enzymes cleave chondroitin at specific points by removing certain sugar units, thereby breaking down the large, complex molecule into smaller fragments. Chondroitin lyases are classified based on their site of action and the type of fragment they produce. They play important roles in various biological processes, including tissue remodeling, growth, and development. In some cases, chondroitin lyases may also be used in research and medical settings to study the structure and function of proteoglycans or for the production of smaller chondroitin fragments with therapeutic potential.
Proteoglycans are complex, highly negatively charged macromolecules that are composed of a core protein covalently linked to one or more glycosaminoglycan (GAG) chains. They are a major component of the extracellular matrix (ECM) and play crucial roles in various biological processes, including cell signaling, regulation of growth factor activity, and maintenance of tissue structure and function.
The GAG chains, which can vary in length and composition, are long, unbranched polysaccharides that are composed of repeating disaccharide units containing a hexuronic acid (either glucuronic or iduronic acid) and a hexosamine (either N-acetylglucosamine or N-acetylgalactosamine). These GAG chains can be sulfated to varying degrees, which contributes to the negative charge of proteoglycans.
Proteoglycans are classified into four major groups based on their core protein structure and GAG composition: heparan sulfate/heparin proteoglycans, chondroitin/dermatan sulfate proteoglycans, keratan sulfate proteoglycans, and hyaluronan-binding proteoglycans. Each group has distinct functions and is found in specific tissues and cell types.
In summary, proteoglycans are complex macromolecules composed of a core protein and one or more GAG chains that play important roles in the ECM and various biological processes, including cell signaling, growth factor regulation, and tissue structure maintenance.
Articular cartilage is the smooth, white tissue that covers the ends of bones where they come together to form joints. It provides a cushion between bones and allows for smooth movement by reducing friction. Articular cartilage also absorbs shock and distributes loads evenly across the joint, protecting the bones from damage. It is avascular, meaning it does not have its own blood supply, and relies on the surrounding synovial fluid for nutrients. Over time, articular cartilage can wear down or become damaged due to injury or disease, leading to conditions such as osteoarthritis.
Collagen type XVIII is a type of collagen that is found in the basement membrane, which is a thin layer of extracellular matrix that separates and supports epithelial and endothelial cells. It is a heterotrimeric protein composed of three different chains, alpha1(XVIII), alpha2(XVIII), and alpha3(XVIII). Collagen XVIII is thought to play a role in the maintenance and organization of the basement membrane, as well as in cell adhesion and migration. It also contains a number of distinct domains that are involved in various biological processes, including angiogenesis, tissue repair, and tumor growth. Mutations in the gene that encodes collagen XVIII have been associated with eye diseases such as Knobloch syndrome and familial exudative vitreoretinopathy.
Procollagen is the precursor protein of collagen, which is a major structural protein in the extracellular matrix of various connective tissues, such as tendons, ligaments, skin, and bones. Procollagen is synthesized inside the cell (in the rough endoplasmic reticulum) and then processed by enzymes to remove specific segments, resulting in the formation of tropocollagen, which are the basic units of collagen fibrils.
Procollagen consists of three polypeptide chains (two alpha-1 and one alpha-2 chain), each containing a central triple-helical domain flanked by non-helical regions at both ends. These non-helical regions, called propeptides, are cleaved off during the processing of procollagen to tropocollagen, allowing the individual collagen molecules to align and form fibrils through covalent cross-linking.
Abnormalities in procollagen synthesis or processing can lead to various connective tissue disorders, such as osteogenesis imperfecta (brittle bone disease) and Ehlers-Danlos syndrome (a group of disorders characterized by joint hypermobility, skin hyperextensibility, and tissue fragility).
"Cells, cultured" is a medical term that refers to cells that have been removed from an organism and grown in controlled laboratory conditions outside of the body. This process is called cell culture and it allows scientists to study cells in a more controlled and accessible environment than they would have inside the body. Cultured cells can be derived from a variety of sources, including tissues, organs, or fluids from humans, animals, or cell lines that have been previously established in the laboratory.
Cell culture involves several steps, including isolation of the cells from the tissue, purification and characterization of the cells, and maintenance of the cells in appropriate growth conditions. The cells are typically grown in specialized media that contain nutrients, growth factors, and other components necessary for their survival and proliferation. Cultured cells can be used for a variety of purposes, including basic research, drug development and testing, and production of biological products such as vaccines and gene therapies.
It is important to note that cultured cells may behave differently than they do in the body, and results obtained from cell culture studies may not always translate directly to human physiology or disease. Therefore, it is essential to validate findings from cell culture experiments using additional models and ultimately in clinical trials involving human subjects.
Collagen type X is a specific type of collagen that is primarily found in the hypertrophic zone of mature cartilage, which is located near the site of bone formation during endochondral ossification. It plays a crucial role in the mineralization process of the cartilage matrix and is essential for the formation of healthy bones. Collagen type X is composed of three identical alpha chains that form a triple helix structure, and it is synthesized by chondrocytes, which are the specialized cells found in cartilage tissue. Mutations in the gene that encodes collagen type X have been associated with certain skeletal disorders, such as Schmid metaphyseal chondrodysplasia.
Matrilin proteins are a group of extracellular matrix (ECM) proteins that are predominantly found in cartilaginous tissues, such as articular cartilage, costal cartilage, and intervertebral discs. They belong to the von Willebrand factor A (vWF-A) domain-containing protein family and play important roles in maintaining the structural integrity and organization of the ECM.
Matrilin proteins are composed of multiple domains, including vWF-A domains, coiled-coil domains, and calcium-binding epidermal growth factor (cbEGF)-like domains. They can form multimeric complexes through their coiled-coil domains, which helps to stabilize the ECM network.
There are four known matrilin proteins in humans, designated as Matrilin-1, Matrilin-2, Matrilin-3, and Matrilin-4. Each of these proteins has distinct tissue distribution patterns and functions. For example, Matrilin-1 is primarily found in hyaline cartilage and is involved in regulating chondrocyte differentiation and matrix assembly. Matrilin-2 is widely expressed in various tissues, including cartilage, tendon, and ligament, and plays a role in maintaining the organization of collagen fibrils. Matrilin-3 is specifically expressed in articular cartilage and is involved in regulating the formation and maintenance of the cartilaginous matrix. Matrilin-4 is found in both hyaline and fibrocartilage, as well as in tendons and ligaments, and has been implicated in regulating collagen fibrillogenesis and tissue development.
Mutations in matrilin genes have been associated with various musculoskeletal disorders, such as multiple epiphyseal dysplasia (MED) and spondyloepimetaphyseal dysplasia (SEMD). These genetic defects can lead to abnormalities in the structure and organization of the ECM, resulting in joint pain, stiffness, and reduced mobility.
Collagen type XII is a type of collagen that is found in the extracellular matrix of various tissues, including tendons, ligaments, and skin. It is a fibril-associated collagen that is closely associated with collagens type I and III. Collagen type XII has been shown to play a role in regulating the organization and diameter of collagen fibrils. Mutations in the gene for collagen type XII have been associated with certain types of muscular dystrophy and Bethlem myopathy, which are genetic disorders that affect muscle strength and tone. Additionally, it has been suggested to play a role in the development of osteoarthritis.
Fibronectin is a high molecular weight glycoprotein that is found in many tissues and body fluids, including plasma, connective tissue, and the extracellular matrix. It is composed of two similar subunits that are held together by disulfide bonds. Fibronectin plays an important role in cell adhesion, migration, and differentiation by binding to various cell surface receptors, such as integrins, and other extracellular matrix components, such as collagen and heparan sulfate proteoglycans.
Fibronectin has several isoforms that are produced by alternative splicing of a single gene transcript. These isoforms differ in their biological activities and can be found in different tissues and developmental stages. Fibronectin is involved in various physiological processes, such as wound healing, tissue repair, and embryonic development, and has been implicated in several pathological conditions, including fibrosis, tumor metastasis, and thrombosis.
Chondrocytes are the specialized cells that produce and maintain the extracellular matrix of cartilage tissue. They are responsible for synthesizing and secreting the collagen fibers, proteoglycans, and other components that give cartilage its unique properties, such as elasticity, resiliency, and resistance to compression. Chondrocytes are located within lacunae, or small cavities, in the cartilage matrix, and they receive nutrients and oxygen through diffusion from the surrounding tissue fluid. They are capable of adapting to changes in mechanical stress by modulating the production and organization of the extracellular matrix, which allows cartilage to withstand various loads and maintain its structural integrity. Chondrocytes play a crucial role in the development, maintenance, and repair of cartilaginous tissues throughout the body, including articular cartilage, costal cartilage, and growth plate cartilage.
Hydroxyproline is not a medical term per se, but it is a significant component in the medical field, particularly in the study of connective tissues and collagen. Here's a scientific definition:
Hydroxyproline is a modified amino acid that is formed by the post-translational modification of the amino acid proline in collagen and some other proteins. This process involves the addition of a hydroxyl group (-OH) to the proline residue, which alters its chemical properties and contributes to the stability and structure of collagen fibers. Collagen is the most abundant protein in the human body and is a crucial component of connective tissues such as tendons, ligaments, skin, and bones. The presence and quantity of hydroxyproline can serve as a marker for collagen turnover and degradation, making it relevant to various medical and research contexts, including the study of diseases affecting connective tissues like osteoarthritis, rheumatoid arthritis, and Ehlers-Danlos syndrome.
Fibroblasts are specialized cells that play a critical role in the body's immune response and wound healing process. They are responsible for producing and maintaining the extracellular matrix (ECM), which is the non-cellular component present within all tissues and organs, providing structural support and biochemical signals for surrounding cells.
Fibroblasts produce various ECM proteins such as collagens, elastin, fibronectin, and laminins, forming a complex network of fibers that give tissues their strength and flexibility. They also help in the regulation of tissue homeostasis by controlling the turnover of ECM components through the process of remodeling.
In response to injury or infection, fibroblasts become activated and start to proliferate rapidly, migrating towards the site of damage. Here, they participate in the inflammatory response, releasing cytokines and chemokines that attract immune cells to the area. Additionally, they deposit new ECM components to help repair the damaged tissue and restore its functionality.
Dysregulation of fibroblast activity has been implicated in several pathological conditions, including fibrosis (excessive scarring), cancer (where they can contribute to tumor growth and progression), and autoimmune diseases (such as rheumatoid arthritis).