Lecture 2

Cartilage Cells

Chondrocytes are the only cells present in cartilage

Chondrocytes sit in the lacunae of the extracellular matrix

• They secrete the extracellular matrix and have a role in its maintenance

These are derived from mesenchymal stem cells

However, the term chondroblast (=prechondrocyte) has been sometimes used to refer to cartilage cells that demonstrate high proliferative behaviour

Cartilage Matrix

Consists of collagen fibres + an amorphous ground substance

• Can either be type I or type II collagen, or elastin fibres

The amorphous extracellular material is composed chiefly of proteoglycans and hyaluronan.

• The proteoglycans are large aggrecan molecules that consist of a core protein and numerous sulphated glycosaminoglycan (GAG) side chains (a type of polysaccharide)

  • GAGs have multiple negative charge, therefore the resulting aggrecan aggregates are extremely hydrophilic and absorb high quantities of water

    • The resulting swelling pressure is counteracted by collagen fibres that resist stretching (tension), resulting in extremely high resistance to compression.

Aggrecans form large aggregates with hyaluronan (a large non-sulphated GAG) called aggrecan aggregates.

Cartilage Nourishment

Cartilage is generally avascular, alymphatic and aneural meaning that there are no vessels or nerves found within cartilage

Therefore, cartilage has to rely on diffusion to take up necessary nutrients and oxygen and to remove waste. This significantly limits how thick cartilage could get and impedes healing following injury

• The further the chondrocytes away from the capillaries, the lower the activity of the cell

  • If cartilage becomes too thick, blood vessels may need within the cartilage (such as during embryonic development)

Types of Cartilage

Hyaline cartilage

Hyaline means glassy which refers to the white colour and transparency of this type of cartilage

Consists of type II collagen

Has a perichondrium

High ratio of GAGs/collagen

Hyaline cartilage is found in:

• respiratory tract (nose, larynx, trachea, bronchi)

• ventral ends of ribs

• articular cartilage (smooth, resilient, frictionless surface)

  • Only one that doesn’t have perichondrium (instead has synovial fluid assists instead but does NOT cover the cartilage itself)

• embryonic cartilaginous anlagen of bones

• growth plates of growing long bones

Elastic cartilage

Consists of type II collagen and elastic fibres → therefore more flexible than hyaline cartilage

Has a perichondrium

High ratio of GAGs/collagen

This type is found in:

• external ear

• epiglottis (part of larynx)

Fibrocartilage

Consists of type I collagen fibres

There is no perichondrium

Chondrocytes usually arranged in columns

Has a low ratio of GAGs/collagen = more collagen then aggregtes and GAG’s

Fibrocartilage is found in:

• intervertebral discs

• menisci

• points of attachment of tendons and ligaments to bone

• cardiac skeleton

Cartilage Development

Appositional vs interstitial Growth

Appositional growth occurs when chondroblasts secrete new matrix along existing surfaces (endosteal and periosteal (I think)) and this causes the cartilage to expand and widen.

In interstitial growth, chondrocytes secrete new matrix within the cartilage and this causes it to grow in length.

Cells within the lacunae can still proliferate or enlarge as the surrounding matrix is still quite accommodating unlike that of the bone.

• Proliferation results in occasional pairs (or even more) of chondrocytes within lacunae which leads to ‘interstitial growth’.

• When two or more cells are found within a single lacuna, that lacuna is sometimes called a ‘nest of cells’

Endochondral Ossification

In this mode of ossification, bone formation begins with formation of a cartilage model, followed by formation of a primary centre of ossification

1. Cartilage model is formed

2. Blood vessels appear → bring in nutrients and growth factors

3. Perichondrium turns periosteum

4. Osteoblasts are then formed and a collar of bone is deposited on the surface of the model all around = periosteal bone collar

   • Forms via intramembranous ossification initially

5. Chondrocytes hypertrophy → they become closer → matrix becomes thinner → vessels invade the cartilaginous core → conversion into osteoblasts or apoptosis and replacement with precursors

6. Osteoclasts also arrive and resorb the old (and sometimes mineralised) cartilage matrix

7. Osteoblasts secrete osteoid on the cartilage matrix remnant that survives this initial resorption and works as a scaffold for new bone

8. Chondrocytes in the cartilage model proliferate and secrete more matrix → more chondrocytes are also differentiated from their mesenchymal precursors in the perichondrium adding more cartilage to the periphery. These processes result in more cartilage growth lengthwise

9. Formation of at least one secondary centre of ossification **(most but not all long bones) in epiphyseal cartilage at each end, through a process similar to that for primary centre is responsible for the ossification of epiphyses

A cartilaginous growth plate (=physis) is formed in between the epiphysis and metaphysis during this formation of secondary ossifications.

Growth plates are where expansion and interstitial growth occurs until maturation occurs → growth plates then completely ossify once the metaphysis ossifcation rate takes over → bone stops growing

Regulation of Endochondral Ossification

Proliferation of chondroblasts tend to be stimulated by growth hormones

Hypertrophy of chondrocytes tend to be stimulated by thyroid hormones

VEGF, RANKL and BMPs regulate the behaviour of invading cells, i.e. endothelial cells, osteoblasts, osteoclasts, etc.

• vascular endothelial growth factor (VEGF) stimulates angiogenesis

• BMPs stimulate osteoblast differentiation from bone marrow stromal cells

• receptor activator of NFκB ligand (RANKL) stimulates osteoclast differentiation

Definitions

Perichondrium - a layer of vascular tissue that has an outer fibrous layer (fibroblasts, fibrocytes, and blood vessels) and an inner germinal layer containing chondrogenic precursors (rich in mesenchymal cells and chondroblasts)