Product Code Database
Chondrocytes (, ) are the only cells found in healthy cartilage. They produce and maintain the cartilaginous matrix, which consists mainly of collagen and . 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 .
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 originally undifferentiated mesenchymal stem cells lose their Cell potency, proliferate and crowd together in a dense aggregate of chondrogenic cells (cartilage) at the location of chondrification. These chondrogenic cells differentiate into so-called chondroblasts, which then synthesize the cartilage extracellular matrix (ECM), consisting of a ground substance (proteoglycans, glycosaminoglycans for low osmotic potential) and fibers. The chondroblast is now a mature chondrocyte that is usually inactive but can still secrete and degrade the matrix, depending on conditions.
Cell culture studies of excess Vitamin A inhibits the synthesis of chondroitin sulfate by chondrocytes and causes the inhibition of chondrogenesis in the developing embryo which may result in limb malformations.
Chondrocytes undergo terminal differentiation when they become hypertrophic, which happens during endochondral ossification. This last stage is characterized by major phenotype changes in the cell.
Endochondral ossification is the process by which most vertebrate Axial skeleton form into hardened bones from cartilage. This process begins with a cartilage anlage where chondrocyte cells will congregate and start their maturation process. Once the chondrocytes have fully matured at the desired rate, the cartilage tissue will harden into bone. This process is similar across most vertebrates and is closely regulated due to the large importance of the skeleton in survival. Few deviations, misregulations, and mutations are found in organisms because they are often detrimental or lethal to the organism. This is why chondrocyte maturation is so tightly regulated. If they mature too quickly or slowly there is a large possibility the organism will not survive gestation or infancy. One gene that is closely involved in skeletal formation is Xylt1. Normally, this gene is responsible for catalyzing the addition of glycosaminoglycan (GAG) side chains to Proteoglycan, which are used during cell signaling to control processes such as cell growth, proliferation, and adhesion. The two main proteoglycans that are used in this process are Heparan sulfate (HSPGs) and chondroitin sulfate proteoglycans (CSPGs) which are present at high levels in the chondrocyte extracellular matrix and are crucial in regulating chondrocyte maturation. When the GAG chain functions properly, it controls the maturation speed of chondrocytes and ensures enough cells gather in the cartilage anlage. Xylt1 is an essential gene in regards to chondrocytes and proper skeletal formation, and is a key factor in the close regulation of maturation. However, the mutation pug of the Xylt1 gene was studied in mice in 2014 and was found to cause the pre-maturation of chondrocytes. Animals with homozygous pug alleles display dwarfism and have considerably shorter bones compared to Wild type animals. These organisms show a reduction of typical Xylt1 gene activity, as well as a reduction in GAG chain levels. This mutation causes fewer GAG chains to be added to HSPGs and CSPGs, meaning there are fewer complexes available to closely regulate the maturation of chondrocytes. Incorrect signals are sent to chondrocytes in the cartilage anlage because the GAG chain and proteoglycan complexes are unable to work properly and cause the chondrocytes to mature and ossify too quickly. The correct amount of chondrocytes are not able to gather in the cartilage anlage, leading to a shortage of cartilage for ossification and eventually shorter bones.
While the pug mutation deals with the pre-maturation of chondrocytes, multiple other mutations alter chondrocyte proliferation. One such example, the point mutation G380R located on the fibroblast growth factor receptor 3(FGFR-3) gene leads to achondroplasia, a type of dwarfism. Achondroplasia is either caused through a spontaneous mutation or inherited in an autosomal dominant fashion. Both the homozygous dominant and the heterozygous genotypes exhibit achondroplasia symptoms, but the heterozygotes are often milder. Individuals with the mutated allele(s) display a variety of symptoms of the failure of endochondral ossification, including the shortening of proximal long limbs and midface hypoplasia. The non-mutated FGFR-3 gene is responsible for the expression of fibroblast growth factors(FGFs) which has to maintain a certain level to ensure that the proliferation of chondrocytes happens accordingly. The G380R mutation causes FGFR-3 to over express FGFs and the balance within the cartilage extracellular matrix is thrown off. Chondrocytes will proliferate too quickly and disrupt the assembly at the cartilage anlage and detrimentally alter the formation of bone. This mutation acts in a dosage fashion, meaning that when only one copy is present, there is still an uptake in FGF expression, but less so than when there are two copies of the mutation.
In Australia, Ortho-ACI, a suspension of cultured autologous chondrocytes, is [[indicated]] for use in the treatment of cartilage lesions associated with the knee, patella, and ankle.
==Gallery==
|
|
