Chondrogenesis is the process by which

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 an ...

is developed.

Cartilage in fetal development

embryogenesis An embryo is an initial stage of development of a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male sperm ...

, the

skeletal A skeleton is the structural frame that supports the body of an animal. There are several types of skeletons, including the exoskeleton, which is the stable outer shell of an organism, the endoskeleton, which forms the support structure inside ...

system is derived from the

mesoderm The mesoderm is the middle layer of the three germ layers that develops during gastrulation in the very early development of the embryo of most animals. The outer layer is the ectoderm, and the inner layer is the endoderm.Langman's Medical E ...

germ layer. Chondrification (also known as chondrogenesis) is the process by which cartilage is formed from condensed

mesenchyme Mesenchyme () is a type of loosely organized animal embryonic connective tissue of undifferentiated cells that give rise to most tissues, such as skin, blood or bone. The interactions between mesenchyme and epithelium help to form nearly every o ...

tissue, which differentiates into

chondrocytes 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 proteog ...

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''.

Mineralization

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. 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 Fusis, Phusis or Physis (; grc, φύσις ) is a Greek philosophical, theological, and scientific term, usually translated into English—according to its Latin translation "natura"—as "nature". The term originated in ancient Greek philosophy, ...

. A ''cement line'' demarcates articular calcified cartilage from subchondral bones.

Repair

Once damaged, cartilage has limited repair capabilities. Because

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, surgeons and scientists have elaborated a series of cartilage repair procedures that help to postpone the need for joint replacement. 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.

Synthetic cartilage

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. 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." 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.

Molecular level

Bone morphogenetic proteins are growth factors released during embryonic development to induce condensation and determination of cells, during chondrogenesis.

Noggin Noggin may refer to: General * Noggin or gill (volume), a unit of volume * Noggin (cup), a small cup * Noggin, slang for head A head is the part of an organism which usually includes the ears, brain, forehead, cheeks, chin, eyes, nose, an ...

, a developmental protein, inhibits chondrogenesis by preventing condensation and differentiation of mesenchymal cells. The molecule

sonic hedgehog Sonic hedgehog protein (SHH) is encoded for by the ''SHH'' gene. The protein is named after the character ''Sonic the Hedgehog''. This signaling molecule is key in regulating embryonic morphogenesis in all animals. SHH controls organogenesis and ...

(Shh) modifies the activation of the L-Sox5,

Sox6 Transcription factor SOX-6 is a protein that in humans is encoded by the ''SOX6'' gene. Function The SOX gene family encodes a group of transcription factors defined by the conserved high mobility group (HMG) DNA-binding domain. Unlike most tr ...

Sox9 Transcription factor SOX-9 is a protein that in humans is encoded by the ''SOX9'' gene. Function SOX-9 recognizes the sequence CCTTGAG along with other members of the HMG-box class DNA-binding proteins. It is expressed by proliferating but no ...

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. 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. The molecule

Indian hedgehog The Indian hedgehog (''Paraechinus micropus'') is a species of hedgehog native to India and Pakistan. It mainly lives in sandy desert areas but can be found in other environments. Description The Indian hedgehog can be compared to the long-ear ...

(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.

Sulfation

The

SLC26A2 The sulfate transporter is a solute carrier family protein that in humans is encoded by the ''SLC26A2'' gene. SLC26A2 is also called the diastrophic dysplasia sulfate transporter (DTDST), and was first described by Hästbacka et al. in 1994. A de ...

is a sulfate transporter. Defects result in several forms of

osteochondrodysplasia Osteochondrodysplasia is a general term for a disorder of the development (dysplasia) of bone ("osteo") and cartilage ("chondro"). Osteochondrodysplasias are rare diseases. About 1 in 5,000 babies are born with some type of skeletal dysplasia. Non ...

References

{{Bone/cartilage physiology Embryology