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Chondrogenesis is the process by which cartilage is developed. [1]
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Chondrogenesis is the process by which cartilage is developed. [1]
In embryogenesis, the skeletal system is derived from the mesoderm germ layer. Chondrification (also known as chondrogenesis) is the process by which cartilage is formed from condensed mesenchyme tissue, [2] which differentiates into chondrocytes and begins secreting the molecules that form the extracellular matrix.
Early in fetal development, the greater part of the skeleton is cartilaginous. This temporary cartilage is gradually replaced by bone (endochondral ossification), a process that ends at puberty. In contrast, the cartilage in the joints remains unossified during the whole of life and is, therefore, permanent.[ citation needed ]
Adult hyaline articular cartilage is progressively mineralized at the junction between cartilage and bone. It is then termed articular calcified cartilage. A mineralization front advances through the base of the hyaline articular cartilage at a rate dependent on cartilage load and shear stress. Intermittent variations in the rate of advance and mineral deposition density of the mineralizing front, lead to multiple "tidemarks" in the articular calcified cartilage.[ citation needed ]
Adult articular calcified cartilage is penetrated by vascular buds, and new bone produced in the vascular space in a process similar to endochondral ossification at the physis. A cement line demarcates articular calcified cartilage from subchondral bones.[ citation needed ]
Once damaged, cartilage has limited repair capabilities. Because chondrocytes are bound in lacunae, they cannot migrate to damaged areas. Also, because hyaline cartilage does not have a blood supply, the deposition of new matrix is slow. Damaged hyaline cartilage is usually replaced by fibrocartilage scar tissue. Over the last years[ when? ], surgeons and scientists have elaborated a series of cartilage repair procedures that help to postpone the need for joint replacement.[ citation needed ]
In a 1994 trial, Swedish doctors repaired damaged knee joints by implanting cells cultured from the patient's own cartilage. In 1999, US chemists created an artificial liquid cartilage for use in repairing torn tissue. The cartilage is injected into a wound or damaged joint and will harden with exposure to ultraviolet light. [3]
Researchers say their lubricating layers of "molecular brushes" can outperform nature under the highest pressures encountered within joints, with potentially important implications for joint replacement surgery. [4] Each 60-nanometre-long brush filament has a polymer backbone from which small molecular groups stick out. Those synthetic groups are very similar to the lipids found in cell membranes.
"In a watery environment, each of these molecular groups attracts up to 25 water molecules through electrostatic forces, so the filament as a whole develops a slick watery sheath. These sheathes ensure that the brushes are lubricated as they rub past each other, even when firmly pressed together to mimic the pressures at bone joints." [4]
Known as double-network hydrogels, the incredible strength of these new materials was a happy surprise when first discovered by researchers at Hokkaido in 2003. Most conventionally prepared hydrogels - materials that are 80 to 90 percent water held in a polymer network - easily break apart like a gelatin. The Japanese team serendipitously discovered that the addition of a second polymer to the gel made them so tough that they rivaled cartilage - tissue which can withstand the abuse of hundreds of pounds of pressure. [5]
Bone morphogenetic proteins are growth factors released during embryonic development to induce condensation and determination of cells, during chondrogenesis. [6] Noggin, a developmental protein, inhibits chondrogenesis by preventing condensation and differentiation of mesenchymal cells. [6]
The molecule sonic hedgehog (Shh) modifies the activation of the L-Sox5, Sox6, Sox9 and Nkx3.2. Sox9 and Nkx3.2 induce each other in a positive feedback loop where Nkx3.2 inactivates a Sox9 inhibitor. This loop is supported by BMP expression. The expression of Sox9 induces the expression of BMP, which causes chondrocytes to proliferate and differentiate. [7]
L-Sox5 and Sox6 share this common role with Sox9. L-Sox5 and Sox6 are thought to induce the activation of the Col2a1 and the Col11a2 genes, and to repress the expression of Cbfa1, a marker for late stage Chondrocytes. L-Sox5 is also thought to be involved primarily in embryonic chondrogenesis, while Sox6 is thought to be involved in post-natal chondrogenesis. [8]
The molecule Indian hedgehog (Ihh) is expressed by prehypertrophic chondrocytes. Ihh stimulates chondrocyte proliferation and regulates chondrocyte maturation by maintaining the expression of PTHrP. PTHrP acts as a patterning molecule, determining the position in which the chondrocytes initiate differentiation. [9]
Research is still ongoing and novel transcription factors, such as ATOH8 and EBF1, are added to the list of genes that regulate chondrogenesis. [10]
The SLC26A2 is a sulfate transporter. Defects result in several forms of osteochondrodysplasia. [11]
Cartilage is a resilient and smooth type of connective tissue. It is a semi-transparent and non-porous type of tissue. It is usually covered by a tough and fibrous membrane called perichondrium. 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. It usually grows quicker than bone.
Osteoblasts are cells with a single nucleus that synthesize bone. However, in the process of bone formation, osteoblasts function in groups of connected cells. Individual cells cannot make bone. A group of organized osteoblasts together with the bone made by a unit of cells is usually called the osteon.
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.
Chondrocytes 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 can differentiate into various cell types, including osteoblasts.
Chondroblasts, or perichondrial cells, is the name given to mesenchymal progenitor cells in situ which, from endochondral ossification, will form chondrocytes in the growing cartilage matrix. Another name for them is subchondral cortico-spongious progenitors. They have euchromatic nuclei and stain by basic dyes.
Articular cartilage, most notably that which is found in the knee joint, is generally characterized by very low friction, high wear resistance, and poor regenerative qualities. It is responsible for much of the compressive resistance and load bearing qualities of the knee joint and, without it, walking is painful to impossible. Osteoarthritis is a common condition of cartilage failure that can lead to limited range of motion, bone damage and invariably, pain. Due to a combination of acute stress and chronic fatigue, osteoarthritis directly manifests itself in a wearing away of the articular surface and, in extreme cases, bone can be exposed in the joint. Some additional examples of cartilage failure mechanisms include cellular matrix linkage rupture, chondrocyte protein synthesis inhibition, and chondrocyte apoptosis. There are several different repair options available for cartilage damage or failure.
Chondroblastoma is a rare, benign, locally aggressive bone tumor that typically affects the epiphyses or apophyses of long bones. It is thought to arise from an outgrowth of immature cartilage cells (chondroblasts) from secondary ossification centers, originating from the epiphyseal plate or some remnant of it.
Growth differentiation factor 6 (GDF6) is a protein that in humans is encoded by the GDF6 gene.
An isogenous group is a cluster of up to eight chondrocytes found in hyaline and elastic cartilage.
Indian hedgehog homolog (Drosophila), also known as IHH, is a protein which in humans is encoded by the IHH gene. This cell signaling protein is in the hedgehog signaling pathway. The several mammalian variants of the Drosophila hedgehog gene (which was the first named) have been named after the various species of hedgehog; the Indian hedgehog is honored by this one. The gene is not specific to Indian hedgehogs.
Transcription factor SOX-5 is a protein that in humans is encoded by the SOX5 gene.
Matrilin-3 is a protein that in humans is encoded by the MATN3 gene. It is linked to the development of many types of cartilage, and part of the Matrilin family, which includes Matrilin-1, Matrilin-2, Matrilin-3, and Matrilin-4, a family of filamentous-forming adapter oligomeric extracellular proteins that are linked to the formation of cartilage and bone, as well as maintaining homeostasis after development. It is considered an extracellular matrix protein that functions as an adapter protein where the Matrilin-3 subunit can form both homo-tetramers and hetero-oligomers with subunits from Matrilin-1 which is the cartilage matrix protein. This restricted tissue has been strongly expressed in growing skeletal tissue as well as cartilage and bone.
Transcription factor Sp7, also called osterix (Osx), is a protein that in humans is encoded by the SP7 gene. It is a member of the Sp family of zinc-finger transcription factors It is highly conserved among bone-forming vertebrate species It plays a major role, along with Runx2 and Dlx5 in driving the differentiation of mesenchymal precursor cells into osteoblasts and eventually osteocytes. Sp7 also plays a regulatory role by inhibiting chondrocyte differentiation maintaining the balance between differentiation of mesenchymal precursor cells into ossified bone or cartilage. Mutations of this gene have been associated with multiple dysfunctional bone phenotypes in vertebrates. During development, a mouse embryo model with Sp7 expression knocked out had no formation of bone tissue. Through the use of GWAS studies, the Sp7 locus in humans has been strongly associated with bone mass density. In addition there is significant genetic evidence for its role in diseases such as Osteogenesis imperfecta (OI).
Articular cartilage repair treatment involves the repair of the surface of the articular joint's hyaline cartilage, though these solutions do not perfectly restore the articular cartilage. These treatments have been shown to have positive results for patients who have articular cartilage damage. They can provide some measure of pain relief, while slowing down the accumulation of damage, or delaying the need for joint replacement surgery.
Autologous chondrocyte implantation is a biomedical treatment that repairs damages in articular cartilage. ACI provides pain relief while at the same time slowing down the progression or considerably delaying partial or total joint replacement surgery. The goal of ACI is to allow people suffering from articular cartilage damage to return to their old lifestyle; regaining mobility, going back to work and even practicing sports again.
Osteochondroprogenitor cells are progenitor cells that arise from mesenchymal stem cells (MSC) in the bone marrow. They have the ability to differentiate into osteoblasts or chondrocytes depending on the signalling molecules they are exposed to, giving rise to either bone or cartilage respectively. Osteochondroprogenitor cells are important for bone formation and maintenance.
Autologous matrix-induced chondrogenesis (AMIC) is a treatment for articular cartilage damage. It combines microfracture surgery with the application of a bi-layer collagen I/III membrane. There is tentative short to medium term benefits as of 2017.
Nasal chondrocytes (NC) are present in the hyaline cartilage of the nasal septum and in fact are the only cell type within the tissue. Similar to chondrocytes present in articular cartilage, NC express extracellular matrix proteins such as glycosaminoglycans and collagen.
Artificial cartilage is a synthetic material made of hydrogels or polymers that aims to mimic the functional properties of natural cartilage in the human body. Tissue engineering principles are used in order to create a non-degradable and biocompatible material that can replace cartilage. While creating a useful synthetic cartilage material, certain challenges need to be overcome. First, cartilage is an avascular structure in the body and therefore does not repair itself. This creates issues in regeneration of the tissue. Synthetic cartilage also needs to be stably attached to its underlying surface i.e. the bone. Lastly, in the case of creating synthetic cartilage to be used in joint spaces, high mechanical strength under compression needs to be an intrinsic property of the material.
Joints form during embryonic development in conjunction with the formation and growth of the associated bones. The joints and bones are developed from the embryonic tissue called mesenchyme.