sign in sign up
<<
Home , Cartilage, Elastic cartilage, Fibrocartilage, Ground substance, Lacuna (histology)

Module 1.6:

N. Swailes, Ph.D. Department of and Cell Biology Rm: B046A ML Tel: 5-7726 E-mail: [email protected]

Required reading

Mescher AL, Junqueira’s Basic Text and , 12th Edition, Chapter 7: pp114-120 Ross MH and Pawlina W, Histology: A Text and Atlas, 6th Edition, Chapter 7: pp198-216

Learning objectives

1) Describe the components and organization of a typical cartilage (hyaline) and outline the mechanical properties each imparts to the tissue.

2) Comment on the similarities and differences between the cellular and extracellular components of cartilage and the other basic connective tissues you have seen.

3) Comment on the supply and waste removal to/from cartilage.

4) Classify, compare and contrast the organization, location and function of the four different types of cartilage. How is each suited to the location it occupies?

5) Outline the processes of cartilage formation () and discuss its growth and repair.

1 | Page Swailes 2 2 | Part General Organizatio A2. General A1. Introduction Page A3. CartilageExtracellular Type I VI Type Type X Type XI abundant) (most Type II type Collagen . iscalled type ofcartilage they maintain.Themain that matrix theextracellular (spaces)within lacunae chondrocytesthatsitin called composed ofcells connectivetissue.Itis aspecialized is Cartilage embedded fibers composedofcollagen is The ECMofcartilage but pliabl substance. Thesecomponentsmaketh rganization of Cartilage A: GeneralOrganization found in largequantities in in found that noted be should It listed. not associated cartilagewith in small amounts arethat types. cartilages that There are four types cartilageof specific

form a3 e.

-

D meshwork of fibrils within all fibrils within meshwork of D

i

n Thereare other typescollagen of richg aproteoglycan I Forms dense irregular bundles that withstand strong tensile forces. tensile strong that withstand bundles denseirregular Forms in Found theForms region of extracellular around matrix latticeis This forcrucial allowing cartilage resistto compressive forces. Organizes the collagen fibrils a into 3- Regulates sizethe of Type II fibrils In Do matrix extracellular in Function nvolved in attaching these cells to the . extracellular the to theseattachingcells in nvolved n ofCartilage stead withstand es Matrix

not form fibers, therefore not designed to resist strong tensile forces. age. fibrocartil large quantities in quantities large : Collagen is s

e ECMsolid forces accompanying intermittent pressure. intermittent accompanying forces round

fib rocartilage

.

D D Extracellular matrix cartilage, the cartilage type of most common in the body. meshwork

only Figure: .

Chart showing the composition of hyaline hyaline of composition the showing Chart .

s

Swailes

A4. Cartilage Extracellular Matrix: Ground substance Ground substance is an amorphous gel-like substance within which the cells and fibers of connective tissues are embedded. In cartilage it is composed of: i. molecules Aggrecan is a that has a very strong Chondroitin affinity for water (hydrophilic). A proteoglycan sulfate consists of non-branching polysaccharide chains called (GAGs) that are bound to a core. Each aggrecan molecule contains many and keratan sulfate chains (GAGs). Protein ii. Hyaluronan () core Is a special GAG that does not bind to a protein core, instead it is a long and linear molecule. In cartilage it binds many aggrecan molecules along its length to form proteoglycan aggregates.

iii. Proteoglycan aggregates The proteoglycan aggregates bind to the collagen fibrils in the ECM and become trapped within the 3-D hexagonal lattice of fibers. This arrangement of hydrophilic proteoglycan aggregates fills the spaces within a collagen meshwork and provides cartilage with its unique ability to cushion and resist compressive forces.

iv. Chondronectin Chondronectin is a cartilage specific . Remember the Hyaluronan glycoprotein laminin and how it was involved in anchoring the epithelium to the basal lamina? In a similar way to laminin, the glycoprotein chondronectin binds the cartilage cells () to the collagen fibrils of the ECM in cartilage.

Chondrocyte

Hyaluronan

Collagen fibril (Type II)

Aggrecan molecule (proteoglycan) A5. Cartilage cells Cartilage also contains cells that synthesize and become embedded in the ECM. There are two major cell types found in cartilage: Chondrocyte • Chondroblasts are located in the , an area of dense irregular Isogenous group that surrounds all types of cartilage (except articular cartilage). These cells form a population that divide and secrete the ECM (fibers and ground substance). Once a has synthesized enough ECM to become surrounded in it own secretions it matures to form a chondrocyte.

• Chondrocytes Chondrocytes are mature cartilage cells. They Chondroblast are mitotic during growth, but this becomes limited in adult tissue. Those cells that have undergone division within the matrix are organized into clusters of cells called Inactive p isogenous groups. As the newly divided cell produces matrix it becomes surrounded and the cell clusters are pushed further apart. The erichondrium spaces within the matrix that the chondrocytes occupy are called lacunae.

A6. Perichondrium

Cartilage is surrounded by a dense irregular connective tissue called the perichondrium (except articular and ). It is essential for appositional growth and maintenance of the Chondrocyte underlying cartilage.

During active appositional growth (see later) it is ii composed of: Chondroblast

i. An outer fibrous perichondrium composed of dense irregular Type I collagen bundles and i (predominates in non-growing cartilage).

ii. An inner chondrogenic layer of cells that divide to form chondroblasts which Fibroblast 4 | Page differentiate to form chondrocytes. A7. Blood Supply to Cartilage

Cartilage is avascular which poses a number of problems:

1. How do chondrocytes receive nutrients and remove waste products? i. Chondrocytes respire under low oxygen tension and metabolize glucose by anaerobic glycolysis to produce lactic acid. ii. The large ratio of proteoglycan to collagen fibers in Matrix cartilage allows more easily through the H O 2 expands ECM from blood vessels within the perichondrium. iii. The hydrophilic nature of the proteoglycan rich ECM draws water and nutrients into the cartilage. When compressive forces are applied to the cartilage, this forces water (and waste products out) just like water can be sucked up and squeezed out of a sponge. 2. How does an avascular cartilage grow with the body? The limitations of getting nutrients to a cellular tissue without a direct blood supply limit the thickness to which cartilage can Compression grow. 3. How does an avascular cartilage repair itself if damaged? H2O It can’t (more later!)

A8. Cartilage Function The 3-D hexagonal lattice created by the meshwork of collagen fibers is filled with hydrophilic . When fully hydrated, the large water content of the ECM acts as a shock absorber and resists the compressive forces that are applied to its surface.

Part B: Types of cartilage B1. Hyaline cartilage Appearance Hyaline cartilage has a glassy appearance in life [Gr. Hyalos = glassy]. Composition and organization Note that the general organization previously was based on hyaline cartilage. The only exception is the specialized hyaline cartilage “articular cartilage”, which lacks a perichondrium. Locations It is the most common form of cartilage found: - in the - lining articular surfaces - in the ribs (costal cartilages) - in the epiphyseal plates (see Development) - forming the temporary of the fetus (see Bone Development ) 5 | Page B2. Articular cartilage

Appearance Articular cartilage is a specialized form of hyaline cartilage that lines the surfaces of . It is different from the other types of hyaline cartilage in the body because it lacks a perichondrium on all aspects. It is a remnant of the original cartilage model of the developing bone. Composition and organization

Articular cartilage has four zones:

1. Tangential zone Chondrocytes are flattened and surrounded by organized Type II collagen fibers arranged in fasicles parallel to the free surface.

2. Transitional zone Chondrocytes are round and randomly distributed within the ECM. Collagen fibers are less well organized in this region.

3. Radial zone Chondrocytes are small, round and organized into short columns perpendicular to the free surface. The collagen fibers are aligned perpendicular to the long axis of the bone.

4. Calcified zone This region has a calcified matrix and is seperated from the radial zone by a calcified line or tidemark. Chondrocytes above this line are the source of cells for growth and renewal. 1

1

2 2

3 3

4

Tidemark Bone

6 | Page 4 B3.

Chondrocyte Appearance Distinctive appearance due to the high fiber Elastin fibers content of the ECM.

Composition and organization Similar to hyaline cartilage except the ECM contains a large quantity of branching elastin fibers interspersed among the collagen fibers. As a result, this type of cartilage is highly flexible and subsequent deformation results in recoil to its original shape and position. Note that elastic cartilage has a perichondrium.

Locations Elastic cartilage is found in the: - of the - auditory tubes - of the

B4. Fibrocartilage Perichondrium

Appearance Intermediate to dense connective tissue and hyaline cartilage. It has a characteristic fibrous Chondrocyte appearance (due to high collagen content) with typical chondrocytes dispersed throughout the ECM.

Composition and organization The ECM contains many Type I collagen fibers Collagen fibers (dense connective tissues) and Type II collagen (hyaline cartilage) organized in parallel bundles oriented in the direction upon which tensile forces act. This hybrid composition makes it ideal for situations where there needs to be resistance to both compression and tensile forces. Note that there is no distinct perichondrium in fibrocartilage and the chondrocytes are often stacked and forced peripheral to fiber bundles.

Locations Fibrocartilage is found in the: - intervertebral discs - pubis 7 | Page - articular disc of SCJ and TMJ Swailes - bone- junction Part C: Chondrogenesis, growth and repair C1. Chondrogenesis i. Mesenchymal cells derived from embryonic will from cartilage. ii. The mesenchymal cells round up, retract their extensions and multiply rapidly to form cellular condensations called chondrification centers that i ii differentiate to form chondroblasts. iii. The chondroblasts begin to synthesize ECM which is deposited around the cells separating them out from one another. iv. The chondroblasts continue to divide to create isogenous groups. As the cartilage matures the mitotic activity decreases and the cells form chondrocytes.

This development process begins centrally and moves outwards, so the most immature cells lie peripherally. iii iv

The growth is known as interstitial growth (see below). The superficial mesenchymal cells form perichondrium. Figure: Chondrogenesis. ECM is deposited by C2. Appositional v Interstitial Growth interstitial growth within chondrification centers.

Once ECM secretion has begun, cartilage continues to grow by a combination of processes: i. Interstitial growth New cartilage is formed by adding new ECM Chondrocyte within the existing cartilage mass. Existing chondrocytes within the cartilage divide in their lacunae and the daughter cells begin to

secrete ECM. This type of growth results in Chondroblast formation of isogenous groups. The events that occur during chondrogenesis (above) are an example of this growth type. ii. Appositional growth New cartilage is formed by adding ECM at the surface of an existing cartilage. The cells responsible for this type of growth are Fibroblast located in the chondrogenic perichondrium (ii). Initially they resemble fibroblasts but when cartilage growth is initiated they divide to form Figure: Appositional growth. Cells in the rounded chondroblasts which begin to secrete perichondrium differentiate and lay down new ECM. Chondroblasts become surrounded by ECM ECM peripherally and mature to form chondrocytes in lacunae. 8 | Page Swailes C3. Cartilage Repair

Cartilage has limited capacity for repair.

When cartilage is damaged it does not heal well because: - the tissue is avascular and rich nutrient supply is needed for energy demanding repair - the cells are relatively immobile so cannot migrate to area of damage - mature chondrocytes are slow/unable to proliferate so can't divide once they get there

If the injury involves the perichondrium can some degree of repair occurs but the defect is also replaced not with new hyaline cartilage but with irregular lumps of fiborcartilage and fibrous connective tissue a process known as (e.g cauliflower ear)

This inability to heal poses a problem in major surgeries where cartilage must be cut during the procedure (e.g. coronary bypass surgery).

9 | Page Swailes