Oligomeric Matrix Protein Involved in Limb Development
Oligomeric Matrix Protein Involved in Limb Development
As a member of the thrombospondin gene family, cartilage oligomeric protein (COMP) is found mainly in the extracellular matrix often associated with cartilage tissue. COMP exhibits a wide binding repertoire and has been shown to be involved in the regulation of chondrogenesis in vitro. Not much is known about the role of COMP in human cartilage tissue in vivo. With the help of immunohistochemistry, Western blot, in situ hybridization, and real-time reverse transcription-polymerase chain reaction, we aimed to elucidate the role of COMP in human embryonic, adult healthy, and osteoarthritis (OA) cartilage tissue. COMP is present during the earliest stages of human limb maturation and is later found in regions where the joints develop. In healthy and diseased cartilage tissue, COMP is secreted by the chondrocytes and is often associated with the collagen fibers. In late stages of OA, five times the COMP mRNA is produced by chondrocytes found in an area adjacent to the main defect than in an area with macroscopically normal appearance. The results indicate that COMP might be involved in human limb development, is upregulated in OA, and due to its wide binding repertoire, could play a role in the pathogenesis of OA as a factor secreted by chondrocytes to ameliorate the matrix breakdown.
Cartilage oligomeric protein (COMP) is a protein of the extracellular matrix and can be found in human articular cartilage, meniscus, and cruciate ligament and tendon. Lower concentrations of COMP can also be detected in hyaline cartilage of the human rib and trachea. It has also been extracted from animal skeletal tissues, such as bovine tendon and mouse, rat, and porcine cartilage. COMP is an anionic, approximately 550-kDa disulfide-linked pentameric glycoprotein and, as a member of the thrombospondin gene family, is also called thrombospondin 5. Epidermal growth factor-like and calcium-binding repeats are located in the central region of the protein. The function of COMP is still not completely understood, but it binds to chondrocytes in vitro. COMP has been shown to bind to matrilins and collagen types I, II, and IX. In contrast, COMP has no affinity to the other members of the thrombospondin family. The DNA-binding protein SP1 regulates COMP expression and also mechanical compression of chondrocytes. COMP expression has been shown to be inhibited by leukemia/lymphoma-related factor (LRF). The human COMP gene is located on chromosome 19. Mutations of this gene can cause pseudoachondroplasia and multiple epiphysial dysplasia. Furthermore, COMP has been shown to be upregulated after traumatic knee injury and has been implicated in the pathogenesis of rheumatoid arthritis and osteoarthritis (OA). During mouse development, COMP staining has been described around maturing articular chondrocytes, and during rat development it has been associated mainly with the growth plate. Fang and colleagues detected COMP as early as day 10 in murine development in the condensing mesenchyme, and later it was found in the growth plate and superficially in the developing joint cartilage. At the time of birth, COMP has been detected in the perichondrium, the periosteum, and the hypertrophic zone of mouse cartilage. This, as well as in vitro experimental evidence, has suggested that COMP is indispensable for cartilage development, but in contrast COMP knockout mice do not show an obvious skeletal phenotype. There are no published results on the role of COMP during human embryonic development. A single 21-week-old human foetus has been investigated for COMP. We therefore aimed to localize COMP during embryonic human limb development, describe it in adult healthy articular cartilage, and then compare its occurrence in healthy cartilage with that of diseased cartilage from late stages of OA.
As a member of the thrombospondin gene family, cartilage oligomeric protein (COMP) is found mainly in the extracellular matrix often associated with cartilage tissue. COMP exhibits a wide binding repertoire and has been shown to be involved in the regulation of chondrogenesis in vitro. Not much is known about the role of COMP in human cartilage tissue in vivo. With the help of immunohistochemistry, Western blot, in situ hybridization, and real-time reverse transcription-polymerase chain reaction, we aimed to elucidate the role of COMP in human embryonic, adult healthy, and osteoarthritis (OA) cartilage tissue. COMP is present during the earliest stages of human limb maturation and is later found in regions where the joints develop. In healthy and diseased cartilage tissue, COMP is secreted by the chondrocytes and is often associated with the collagen fibers. In late stages of OA, five times the COMP mRNA is produced by chondrocytes found in an area adjacent to the main defect than in an area with macroscopically normal appearance. The results indicate that COMP might be involved in human limb development, is upregulated in OA, and due to its wide binding repertoire, could play a role in the pathogenesis of OA as a factor secreted by chondrocytes to ameliorate the matrix breakdown.
Cartilage oligomeric protein (COMP) is a protein of the extracellular matrix and can be found in human articular cartilage, meniscus, and cruciate ligament and tendon. Lower concentrations of COMP can also be detected in hyaline cartilage of the human rib and trachea. It has also been extracted from animal skeletal tissues, such as bovine tendon and mouse, rat, and porcine cartilage. COMP is an anionic, approximately 550-kDa disulfide-linked pentameric glycoprotein and, as a member of the thrombospondin gene family, is also called thrombospondin 5. Epidermal growth factor-like and calcium-binding repeats are located in the central region of the protein. The function of COMP is still not completely understood, but it binds to chondrocytes in vitro. COMP has been shown to bind to matrilins and collagen types I, II, and IX. In contrast, COMP has no affinity to the other members of the thrombospondin family. The DNA-binding protein SP1 regulates COMP expression and also mechanical compression of chondrocytes. COMP expression has been shown to be inhibited by leukemia/lymphoma-related factor (LRF). The human COMP gene is located on chromosome 19. Mutations of this gene can cause pseudoachondroplasia and multiple epiphysial dysplasia. Furthermore, COMP has been shown to be upregulated after traumatic knee injury and has been implicated in the pathogenesis of rheumatoid arthritis and osteoarthritis (OA). During mouse development, COMP staining has been described around maturing articular chondrocytes, and during rat development it has been associated mainly with the growth plate. Fang and colleagues detected COMP as early as day 10 in murine development in the condensing mesenchyme, and later it was found in the growth plate and superficially in the developing joint cartilage. At the time of birth, COMP has been detected in the perichondrium, the periosteum, and the hypertrophic zone of mouse cartilage. This, as well as in vitro experimental evidence, has suggested that COMP is indispensable for cartilage development, but in contrast COMP knockout mice do not show an obvious skeletal phenotype. There are no published results on the role of COMP during human embryonic development. A single 21-week-old human foetus has been investigated for COMP. We therefore aimed to localize COMP during embryonic human limb development, describe it in adult healthy articular cartilage, and then compare its occurrence in healthy cartilage with that of diseased cartilage from late stages of OA.
