Cartilage

Cartilage is a specialized form of connective tissue. It is firm but is more flexible than bone. It is made of cartilage cells and cartilage matrix. Cartilage is devoid of blood vessels. As thus, it depends on surrounding tissues to obtain nutrients and oxygen. This limits its thickness. Very thick (e.g. costal cartilage), have canals that convey blood vessels into the cartilage center. Cartilage is made of cells and an extracellular matrix made fibers embedded in a ground substance. The cartilage is covered by a connective tissue capsule called the perichondrium (absent in fibrocartilage). There are 3 types of cartilage

1. Hyaline cartilage is the most common type of cartilage

2. Elastic cartilage is less common

3. Fibrocartilage is the least common

Hyaline Cartilage

Hyaline cartilage is the most abundant type of cartilage; it is present in the fetal skeleton, respiratory passages, ribs and articular surfaces of synovial joints. It has a bluish tinge when fresh. It is surrounded by a CT investment called the perichondrium. The matrix of hyaline cartilage consists of the ground substance and collagen fibrils (type 2 collagen fibrils). The matrix appears homogenous because the refractive index of the ground substance is about the same as that of the type 2 fibrils. It stains basophilic because it is rich in chondroitin sulfate (a GAG). It is avascular; nutrition reaches cartilages cells by diffusion from blood vessels present in the perichondrium. Precipitation of Ca++ Prohibits diffusion and deprives chondrocytes of nutrition leading to degeneration (regression of cartilage).

The perichondrium

Hyaline cartilage is invested by a connective tissue covering called the perichondrium, The perichondrium has as an inner chondrogenic layer an outer fibrous layer. It contains BVs & nerves. The perichondrium is not present in articular cartilage (has smoother surface). The perichondrium has two layer. The outer layer is made of irregular dense connective tissue predominantly made of type 1 collagen fibers and fibroblasts. It contains the blood vessels and nerves that supply the cartilage. The inner layer is made of loose connective tissue. It is a chondrogenic layer that actively participates in the formation of new cartilage. It contains chondroblast but there are no lacunae in it. It also contains numerous small blood vessels, capillaries and nerves. These blood vessels nourish the cartilage which is devoid of blood vessels i.e. the perichondral vessels are the source of nutrients to the cartilage.    

Fig. 1. An H&E-stained histological section (left) of a hyaline cartilage showing the inner perichondrium, which is a loose connective tissue that covers the cartilage surface; it contains blood vessels (capillaries) and nerves.  The cartilage matrix appears homogenous and basophilic (purple color). The illustration (right) shows fibroblasts in the outer perichondrium, chondroblast in the inner perichondrium, and chondrocyte within lacunae in the cartilage.

Cartilage Cells

Hyaline cartilage contains chondroblasts and chondrocytes. Chondroblasts are young cartilage cells that develop from mesenchymal cells. They often appear round in shape and occur in clusters. They synthesize matrix and become separated by small amounts of matrix. They have many organelles including rER. Chondrocytes are mature chondroblasts entrapped in the matrix. The potential spaces they occupy are called lacunae. Active chondroblasts and chondrocytes have many cisternae of rER, Golgi apparatus, lipid droplets and glycogen particles. Chondrocytes maintain the integrity of the matrix

Chondrocytes an Chondroblasts

Cartilage as a tissue, contains only one type of cells known as chondrocytes and their precursors which are called chondroblasts. Chondrocyte means cartilage cell (chondros = cartilage, cyte = cell). Chondrocytes develop from mesenchymal cells, which are pluripotent cells that give rise to a wide array of functional cells. Chondrocytes and chondroblast synthesize and secrete components of the cartilage matrix which is essentially made of collagen and proteoglycans. In addition, chondrocytes secrete hydrolytic enzymes such as collagenase and neutral proteinases that degrade the matrix. Accordingly, chondrocytes regulate cartilage formation, growth and degeneration. The shape and size of chondrocytes vary according to their location in the cartilage and their activity.  They may be flat, ellipsoid or spherical in shape and their diameter may vary from about 7um to about 30um. The nucleus is often spherical and pale and cytoplasm lightly basophilic. The cytoplasm contains rER, Golgi complex, mitochondria, microtubules and filaments. The potential spaces that chondrocyte occupy with the cartilage are called lacunae (singular lacuna). Chondrocytes fill lacunae, but lacunae can only be seen when chondrocytes shrink for instance due to dehydration during tissue processing for histology. A lacuna usually contains a single chondrocyte except when there is interstitial growth of cartilage where a lacuna contains 2-4 cells forming what are known as cell nests.

Chondroblasts are young immature cartilage cells. They are occasionally referred to as perichondria cells. They are present in the perichondrium and the superficial parts of cartilages. They actively produce components of the cartilage matrix (proteoglycans and collagen). To begin with, they do not occupy lacunae but as they produce more and more matrix, they become trapped within the matrix they produce and thus occupy lacunae. When completely entrapped within the matrix they are called chondrocytes. Both chondroblast and chondrocytes are capable of undergoing mitosis, but the capability of chondroblasts is higher. Chondroblast have a single nucleus; they are mononuclear cells. They are spindle-shaped or polygonal cells with pale oval or spherical nuclei. Chondroblast functions include, cartilage development, cartilage growth, cartilage maintenance and homeostasis of cartilage.

Fig. 2. An H&E-stained histological section and an illustration of hyaline cartilage showing features of chondrocytes and chondroblast. Chondroblasts are flatted cells located within the inner perichondrium whereas chondrocytes are larger ovoid, or spherical cells present within the cartilage and occupy lacunae as single cells or cell nests. 

The Matrix

The matrix of hyaline cartilage is made up of a ground substance and type 2 collagen fibers. Type 2 collagen fibers are thinner than type 1 fibers. They have about the same refractive index as the ground substance and thus cannot be seen under the light microscope in routine histological preparation. This is why the matrix of hyaline cartilage appears amorphous and homogeneous. The name hyaline cartilage has been introduced to reflect this homogeneous glassy appearance of its matrix. Nevertheless, type 2 collagen fibers can be seen in histological sections stained by special methods such as picrosirius red stain and immunohistochemical methods. The ground substance is rich in mucopolysaccharides and accordingly it stains metachromatically with metachromatic stains such as toluidine blue. Mucopolysaccharides are a class of glycoproteins known as proteoglycans. Proteoglycans are made of a protein core to which glycosaminoglycans are attached. Glycosaminoglycans present in proteoglycans of cartilages are of different types, which include chondroitin sulfates, heparan sulfates, keratan sulfate and dermatan sulfate. Proteoglycans are synthesized in the rER of chondroblasts and chondrocytes, then modified in the Golgi apparatus and secreted into the matrix. Proteoglycans play the essential role of hydrating the cartilage matrix by binding themselves to water.

The cartilage matrix is devoid of blood vessels and nerves. Nutrients and oxygen reach chondrocytes within the cartilage from capillaries in the inner perichondrium by diffusion across the matrix. Waste products from these cells reach perichondral capillaries also by diffusion but in the reverse direction. The cartilage is aneural and thus has no sensation; the perichondrium has pain receptors and so any pain associated cartilage pathology is due stimulation of nerve endings present in the perichondrium. 

Elastic Cartilage

Elastic cartilage is less common than hyaline cartilage. It provides both strength and elasticity, and maintains the shapes structures. It is a flexible cartilage that bounces back to its original shape once the force causing flexibility is alleviated. Elastic cartilage is present in non-load-bearing parts of the human body such as the epiglottis, larynx, external ear and the eustachian tube. It resembles hyaline cartilage in all aspects and cannot be differentiated from it in routine histological sections. As in hyaline cartilage, the matrix consists of ground substance made of GAGs and type 2 collagen fibrils. It has chondroblasts and chondrocytes. Chondrocytes are in present lacunae.  The perichondrium has an outer fibrous layer of dense irregular connective tissue an inner chondrogenic layer made of loose connective tissue containing chondroblasts. Both outer and inner layers of perichondrium contain blood vessels and nerve whereas the cartilage itself is avascular and aneural. Elastic cartilage differs from hyaline cartilage in that it contains many branching and anastomosing elastic fibers in its matrix. These elastic fibers can be demonstrated by elastin specific stains such as orcein and aldehyde fuchsin.  

Fig. J3. An illustration (left) and a histological section stained by orcein (right) showing features of elastic cartilage. They show the perichondrium, the matrix, the chondrocytes and the elastic fibers. 

   Fibrocartilage

Fibrocartilage is a tough tissue. It is present in the intervertebral discs, pubic symphyses, and insertions of some ligaments and tendons. It is an intermediate form between dense regular collagenous connective tissue and hyaline cartilage. It is of two variants.

1.      One variant has large bundles of collagen fibers containing small islands of hyaline cartilage in between. It appears like dense connective tissue containing small islands of hyaline cartilage.

2.      The other variant has large flakes of hyaline cartilage separated by smaller bundles of collagen fibers

Fibrocartilage differs from other types of cartilage in that it has no apparent perichondrium.

Fig. J4. An H&E-stained section and an illustration showing features of fibrocartilage, which is made of bundle parallel collagen fibers and flakes of hyaline cartilage in between.

Development and Growth of Cartilage

Cartilage develops from mesenchyme by a process known as chondrogenesis. Under the influence of growth hormone and thyroxine, mesenchymal cells differentiates into chondroblasts, which secrete proteoglycans and collagen type 2 fibers forming the cartilage matrix, gradually entrapping themselves by the matrix they secrete. Once completely entrapped by the matrix they are called chondrocytes. Mesenchyme at the periphery of the newly formed cartilage differentiates into connective tissue cover called the perichondrium. The cartilage formed by chondrogenesis grows by two methods:

1.      Appositional growth, where periosteal chondrogenic cells transform into chondroblasts which lay new cartilage on the surface of the existing old cartilage. Thus the cartilage enlarges by new cartilage building on the surface of old cartilage.

2.      Interstitial growth, where chondrocytes deep in the cartilage matrix proliferate by mitosis and form groups of chondrocytes known as isogenic groups or cell nests. The isogenic group chondrocytes secrete proteoglycans and collagen type 2 fibers forming new matrix around themselves. The cartilage thus grows from within. The newly formed matrix accumulates around chondrocytes and according more basophilic than the old matrix and can easily be identified around lacunae. The newly formed dense perilacunar matrix is known as the territorial matrix. The old matrix which appears paler is called the interterritorial matrix.

Fig. J5. An H&E-stained section of hyaline cartilage undergoing interstitial growth, showing several cell nests. The matrix is amorphous and basophilic. Basophilia is stronger around chondrocytes and cell nests. The illustration on the right shows the territorial matrix and the interterritorial matrix. The territorial matrix is denser.

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