How can solid cartilage grow

These will thicken with the deposition of more osteoid matrix and inorganic salts as the osteoblasts continue their secretion in an appositional manner. This secretion by the osteoblasts is cyclic and results in layers of bone material called lamellae. The deposition of lamellae traps some of the osteoblasts within the osteoid matrix.

Once trapped they are considered mature osteocytes. Osteocytes are characterized by cytoplasmic processes that contact similar processes of adjacent osteocytes.

Gap juctions form at points of contact allowing transfer of small molecules between cells. This transfer is important in co-ordinating bone growth and in the nourishment of osteocytes which may be separated from blood vessels by a considerable amount of calcified bone.

Channals through which cytoplasmic processes of osteocytes extend are called canaliculi. Growing adjacent trabeculae will contact and fuse forming the structure of the mature bone. As intramembranous bones grow, selective reabsorption of bone material is also occurring due to the activities of osteoclast cells. This results in the formation of much of the internal architecture of the bones, providing spaces for blood vessels and marrow.

Most of the bones in the mammalian body are initially formed by endochondral means. This deposition of cartilage occurs as previously discussed and is accomplished by the action of chondroblasts functioning in both interstitial and appositional growth capacities. The typical examples that are used to describe endochondral bone formation are the long bones of the limbs. Perhaps it will be easier to understand their histogenesis if we first consider the general structure of bones.

We will consider this structure as it exists in long bones, however, it should be kept in mind that girdle bones, such as the pelvic girdle, and the intramembranous flat bones of the skull are made up of the same basic components, though they may be arranged somewhat differently.

Bones of the body, including the long bones may be considered a rigid form of connective tissue. The cells of this tissue are embedded within a matrix that consists of organic and inorganic components. The organic matrix, or ground substance, consists of collagen fibers for the most part. While we tend to think of the inorganic components as being the contributing factors in a bone's structural integrity, you should realize that the collagen fibers also contribute significantly to the bones strength and resilience.

Two types of bone tissue can be distingished. These are cancellous, or spongy, bone that lies centrally within the shaft of long bones, and compact or dense bone that lies more peripherally. You should realize that the actual mineralized matrix of these two types of bone is the same. It contains embedded osteocytes that are in communication via gap junctions at their contacting cytoplasmic processes.

The difference between spongy and compact bone lies simply in the size of open spaces within the mineralized bone. The spongy bone consists of slender, irregular trabeculae with large spaces between them where blood vessels, nerves, and marrow cells are located. Compact bone appears solid, no large cavities within it. Since the actual mineralized matrix of both types of bone is the same, there is no distinct boundary between spongy and compact bone.

The shaft of a long bone consists of a medullary or central volume of spongy bone surrounded by a thick cortical layer of compact bone. The compact layer can be subdivided into an outer series of sub-layers called periosteal lamellae that were secreted by the periosteal cells during its development and growth, and an inner component consisting of multiple concentric sub-layers surrounding the halversian canals.

These radial cavities and halversian canals form a network within the compact bone that is continuous with the cavities of the spongy bone. Blood vessels and nerves extend through the channels of this network.

The first step in endochondral bone formation is the histogenesis of a cartilage miniature of the bone. This takes place as discussed above via the action of chondroblasts that have migrated to the area. The chondroblasts secrete a cartilagenous matrix that is laid down both interstitially and appossitionally. The end result is a cartilage template of the bone in miniature that contains chondrocytes embedded within the cartilage matrix.

Actual osteogenesis bone ossification begins with the establishment of a periosteum on the shaft or diaphysis of the cartilage template and the laying down of an intramembranous collar of bone on the circumference of the cartilage diaphysis. This is followed by hypertrophy they get bigger and eventual death of the chondrocytes within the cartilage matrix. As the chondrocytes degenerate they reabsorb some of the surrounding cartilage matrix causing enlargement of the lacunae in which they reside.

This process is known as hypertrophication. As this occurs, the chondrocytes loose their ability to maintain the remaining cartilage matrix and it becomes partially calcified. The end result is an area of porous calcified cartilage within the central regions of the diaphysis. As this is occurring, osteoclasts that have arrived in the area via the circulatory system, begin excavating passageways or tunnels through the intramembranous collar surrounding the diaphysis. These passageways provide a means through which blood vessels, nerves and undifferentiated mesenchymes cells can enter into the lacunae spaces in the remnants of the cartilage matrix that have been left by the degenerating chondrocytes.

The mesenchyme cells will differentiate into osteoblasts and hematopoietic stem cells that are distributed within the bone. The osteoblasts, blood vessels, and nerves form the osteogenic bud that comes to lie more or less centrally within the diaphysis of the forming bone.

As the invading cells spread out within the diaphysis of the cartilage template and ossification begins, this central volume of active bone deposition is called a primary ossification center. The osteoblasts begin to secrete osteoid matrix on the remnants of calcified cartilage. The osteoid matrix becomes mineralized forming cancellous bone in the shaft of the diaphysis. Some of the osteoblasts become trapped within the mineralized bone and become mature bone cells, osteocytes.

As the cancellous bone is layed down, chondroclasts which are the cartilagenous equivalent of osteoclasts reabsorb the calcified cartilage as it is replaced by osteoid matrix i. At this point, it is important to note that this means the actual bone tissue, matrix and mineralization, is the result of the action of a new group of cells, the osteoblasts. The primary ossification center rapidly extends longitudinally within the diaphysis as the shaft of the cartilage template is completely replaced by cancellous bone tissue.

As the ossification center extends longitudinally, so does the calcified outer collar of bone layed down by the periostial osteocytes. As ossification proceeds in the diaphysis, secondary ossification centers form in the cartilage of the bulbuous ends, or epiphyses, at either end of the long bone shaft.

Osteogenic tissues in these regions also act to form mineralized bone. This process is similar to the primary ossification we've just discussed with one difference. Since there is no periosteum on the surface of the epiphyses, there is no periostial external collar of bone.

What we have just discussed is endochondral bone formation. This involved the deposition of cancellous, or spongy bone, within a cartilage matrix.

This is not the final step in bone formation. In fact, there really is no such thing as a final step in this process. During and after endochondral bone formation, there is considerable internal remodeling of the architecture of the bone.

This is accomplished by the efforts of osteoblasts, osteocytes, and osteoclasts. Osteoclasts act to reabsorb much of the cancellous bone that has been layed down during endochondral bone formation. As this occurs, channels are hollowed out within the spongy bone structure. These are in addition to the cavities already formed in spongy bone. In more peripheral regions where compact bone will be present, these channels will give rise to the halversian systems as compact or dense bone is laid down within them.

Most important, articular cartilage has a limited capacity for intrinsic healing and repair. In this regard, the preservation and health of articular cartilage are paramount to joint health. Injury to articular cartilage is recognized as a cause of significant musculoskeletal morbidity. The unique and complex structure of articular cartilage makes treatment and repair or restoration of the defects challenging for the patient, the surgeon, and the physical therapist.

The preservation of articular cartilage is highly dependent on maintaining its organized architecture. Articular cartilage is hyaline cartilage and is 2 to 4 mm thick. Unlike most tissues, articular cartilage does not have blood vessels, nerves, or lymphatics.

It is composed of a dense extracellular matrix ECM with a sparse distribution of highly specialized cells called chondrocytes. The ECM is principally composed of water, collagen, and proteoglycans, with other noncollagenous proteins and glycoproteins present in lesser amounts.

Along with collagen fiber ultrastructure and ECM, chondrocytes contribute to the various zones of articular cartilage—the superficial zone, the middle zone, the deep zone, and the calcified zone Figure 2. Within each zone, 3 regions can be identified—the pericellular region, the territorial region, and the interterritorial region. Schematic, cross-sectional diagram of healthy articular cartilage: A, cellular organization in the zones of articular cartilage; B, collagen fiber architecture.

Copyright American Academy of Orthopaedic Surgeons. Reprinted from the Journal of the American Academy of Orthopaedic Surgeons , ; with permission. The collagen fibers of this zone primarily, type II and IX collagen are packed tightly and aligned parallel to the articular surface Figure 2. The superficial layer contains a relatively high number of flattened chondrocytes, and the integrity of this layer is imperative in the protection and maintenance of deeper layers.

This zone is in contact with synovial fluid and is responsible for most of the tensile properties of cartilage, which enable it to resist the sheer, tensile, and compressive forces imposed by articulation. Immediately deep to the superficial zone is the middle transitional zone, which provides an anatomic and functional bridge between the superficial and deep zones.

In this layer, the collagen is organized obliquely, and the chondrocytes are spherical and at low density. Functionally, the middle zone is the first line of resistance to compressive forces. The deep zone is responsible for providing the greatest resistance to compressive forces, given that collagen fibrils are arranged perpendicular to the articular surface. The deep zone contains the largest diameter collagen fibrils in a radial disposition, the highest proteoglycan content, and the lowest water concentration.

The chondrocytes are typically arranged in columnar orientation, parallel to the collagen fibers and perpendicular to the joint line. The tide mark distinguishes the deep zone from the calcified cartilage. The deep zone is responsible for providing the greatest amount of resistance to compressive forces, given the high proteoglycan content.

Of note, the collagen fibrils are arranged perpendicular to the articular cartilage. The calcified layer plays an integral role in securing the cartilage to bone, by anchoring the collagen fibrils of the deep zone to subchondral bone. In this zone, the cell population is scarce and chondrocytes are hypertrophic.

In addition to zonal variations in structure and composition, the matrix consists of several distinct regions based on proximity to the chondrocytes, composition, and collagen fibril diameter and organization.

The ECM can be divided into pericellular, territorial, and interterritorial regions. The pericellular matrix is a thin layer adjacent to the cell membrane, and it completely surrounds the chondrocyte. It contains mainly proteoglycans, as well as glycoproteins and other noncollagenous proteins. This matrix region may play a functional role to initiate signal transduction within cartilage with load bearing. The territorial matrix surrounds the pericellular matrix; it is composed mostly of fine collagen fibrils, forming a basketlike network around the cells.

The interterritorial region is the largest of the 3 matrix regions; it contributes most to the biomechanical properties of articular cartilage. Proteoglycans are abundant in the interterritorial zone. The chondrocyte is the resident cell type in articular cartilage. Chondrocytes are highly specialized, metabolically active cells that play a unique role in the development, maintenance, and repair of the ECM.

The chondrocytes in the superficial zone are flatter and smaller and generally have a greater density than that of the cells deeper in the matrix Figure 2. Each chondrocyte establishes a specialized microenvironment and is responsible for the turnover of the ECM in its immediate vicinity. This microenvironment essentially traps the chondrocyte within its own matrix and so prevents any migration to adjacent areas of cartilage. Rarely do chondrocytes form cell-to-cell contacts for direct signal transduction and communication between cells.

They do, however, respond to a variety of stimuli, including growth factors, mechanical loads, piezoelectric forces, and hydrostatic pressures.

Chondrocyte survival depends on an optimal chemical and mechanical environment. Several other classes of molecules can be found in smaller amounts in the ECM; these include lipids, phospholipids, noncollagenous proteins, and glycoproteins.

The remainder is contained in the pore space of the matrix. Much of the interfibrillar water appears to exist as a gel, and most of it may be moved through the ECM by applying a pressure gradient across the tissue or by compressing the solid matrix.

The minor collagens help to form and stabilize the type II collagen fibril network. There are at least 15 distinct collagen types composed of no fewer than 29 polypeptide chains. The amino acid composition of polypeptide chains is primarily glycine and proline, with hydroxyproline providing stability via hydrogen bonds along the length of the molecule.

The triple helix structure of the polypeptide chains provides articular cartilage with important shear and tensile properties, which help to stabilize the matrix. Proteoglycans are heavily glycosolated protein monomers. Proteoglycans consist of a protein core with 1 or more linear glycosaminoglycan chains covalently attached.

These chains may be composed of more than monosaccharides; they extend out from the protein core, remaining separated from one another because of charge repulsion. Articular cartilage contains a variety of proteoglycans that are essential for normal function, including aggrecan, decorin, biglycan, and fibromodulin. The largest in size and the most abundant by weight is aggrecan, a proteoglycan that possesses more than chondroitin sulfate and keratin sulfate chains.

Aggrecan is characterized by its ability to interact with hyaluronan HA to form large proteoglycan aggregates via link proteins 12 Figure 3. Aggrecan occupies the interfibrillar space of the cartilage ECM and provides cartilage with its osmotic properties, which are critical to its ability to resist compressive loads. Extracellular matrix of articular cartilage.

Two major load-bearing macromolecules are present in articular cartilage: collagens mainly, type II and proteoglycans notably, aggrecan. Smaller classes of molecules, such as noncollagenous proteins and smaller proteoglycans, are present in smaller amounts.

The interaction between the highly negatively charged cartilage proteoglycans and type II collagen provides the compressive and tensile strength of the tissue. Reprinted with permission from Chen et al, The nonaggregating proteoglycans are characterized by their ability to interact with collagen. Although decorin, biglycan, and fibromodulin are much smaller than aggrecan, they may be present in similar molar quantities. These molecules are closely related in protein structure; however, they differ in glycosaminoglycan composition and function.

Decorin and biglycan possess 1 and 2 dermatan sulfate chains, respectively, whereas fibromodulin possesses several keratin sulfate chains. Decorin and fibromodulin interact with the type II collagen fibrils in the matrix and play a role in fibrillogenesis and interfibril interactions. Biglycan is mainly found in the immediate surrounding of the chondrocytes, where they may interact with collagen VI.

Although a number of noncollagenous proteins and glycoproteins are found within articular cartilage, their specific function has not been fully characterized.

Some of these molecules such as fibronectin and CII, a chondrocyte surface protein likely play a role in the organization and maintenance of the macromolecular structure of the ECM. In adults, the articular cartilage matrix is separated from the subchondral vascular spaces by the subchondral plate. Nutrition of the articular cartilage occurs by diffusion from the synovial fluid. The cartilage matrix restricts materials by size, charge, and molecular configuration.

It is estimated that the average pore size within the ECM is approximately 6. This is in contrast to bone, because bone has a very good blood supply. Cartilage can grow in two ways: Interstitial growth - chondrocytes grow and divide and lay down more matrix inside the existing cartilage.

This mainly happens during childhood and adolescence. Appositional growth - new surface layers of matrix are added to the pre-existing matrix by new chondroblasts from the perichondrium. In children, the cartilaginous plates at the ends of long bones can be seen on X-rays. These templates disappear when adults reach their full height. Constituents of cartilage. Growth and nourishment of cartilage: Unlike other connective tissues cartilage is avascular like epithelia. Cartilage is a flexible connective tissue that differs from bone in several ways.

For one, the primary cell types are chondrocytes as opposed to osteocytes. Chondrocytes are first chondroblast cells that produce the collagen extracellular matrix ECM and then get caught in the matrix. They lie in spaces called lacunae with up to eight chondrocytes located in each.

Chondrocytes rely on diffusion to obtain nutrients as, unlike bone, cartilage is avascular, meaning there are no vessels to carry blood to cartilage tissue. This lack of blood supply causes cartilage to heal very slowly compared with bone. The base substance of cartilage is chondroitin sulfate, and the microarchitecture is substantially less organized than in bone.

The cartilage fibrous sheath is called the perichondrium. The division of cells within cartilage occurs very slowly, and thus growth in cartilage is usually not based on an increase in size or mass of the cartilage itself.

Articular cartilage function is dependent on the molecular composition of its ECM, which consists mainly of proteoglycans and collagens. The remodeling of cartilage is predominantly affected by changes and rearrangements of the collagen matrix, which responds to tensile and compressive forces experienced by the cartilage. Cartilage types: Images of microscopic views of the different types of cartilage: elastic, hyaline, and fibrous.

There are three major types of cartilage: hyaline cartilage, fibrocartilage, and elastic cartilage. Hyaline cartilage is the most widespread cartilage type and, in adults, it forms the articular surfaces of long bones, the rib tips, the rings of the trachea, and parts of the skull.

This type of cartilage is predominately collagen yet with few collagen fibers , and its name refers to its glassy appearance. In the embryo, bones form first as hyaline cartilage before ossifying as development progresses. Hyaline cartilage is covered externally by a fibrous membrane, called the perichondrium, except at the articular ends of bones; it also occurs under the skin for instance, ears and nose.

Hyaline cartilage is found on many joint surfaces. It contains no nerves or blood vessels, and its structure is relatively simple. If a thin slice of cartilage is examined under the microscope, it will be found to consist of cells of a rounded or bluntly angular form, lying in groups of two or more in a granular or almost homogeneous matrix.

These cells have generally straight outlines where they are in contact with each other, with the rest of their circumference rounded.