What are the major components of articular cartilage?
What is the synovium and what is its function?
• Consists of one-three layers of macrophage and fibroblast like cells.
• It produces synovial fluid.
What are the two functions of the synovial fluid?
• Acts as a joint lubricant.
• Provides lubricant for the articular cartilage.
Give 5 characteristics of articular cartilage.
4) No lymphatics
5) No basement membrane
There are four layers or 'zones' to articular cartilage, what are they?
2) Intermediate or middle
4) Calcified cartilage
What is the arrangement of collagen cells in the three most superficial layers of articular cartilage?
1) Superficial layer - Lying flat
2) Intermediate layer - Random assortment
3) Deep layer - Columned
What is the composition of the wet weight of articular cartilage?
• 70% Water
• 20% Collagen
• 7% Proteoglycans
• 2% Cells
• 1% Other proteins
What is the composition of dry weight of articular cartilage?
• 75% Collagen
• 22% Proteoglycans
• 3% Other proteins
What is the percentage composition of the different types of collagens in articular cartilage?
• 94% Type II
• 1% Type VI
• 2% Type IX
• 3% Type XI
What properties does collagen provide for articular cartilage?
Shear and tensile strength.
What are FACITs?
Fibril Associated Collagens with Interupted Triple-Helix
These collagens play an important role in the organisation of fibres within the matrix.
(Type IX is a FACIT collagen, it anchors fibrous type II collagen together.)
What role does Type II cartilage play in articular cartilage? How much of the collagen present is type II?
It is the major fibrous collagen and provides tensile strength.
What is the role of type IX collagen in articular cartilage?
It is a FACIT collagen, it resists shear.
Makes up 2% of the collagen.
What is the role of type VI collagen in articular cartilage?
It is is present in the pericellular matrix, it forms fine fibrils in lacunae around cells.
What role does type XI collagen play in articular cartilage?
Involved in fibril nucleation, i.e. it is inside type II collagen.
What is the major proteoglycan of articular cartilage?
What are the two types of glycosamineglycan found in aggrecan?
• Chondroitin Sulphate
• Keratan Sulphate
What are the functions of proteoglycans in articular cartilage?
1) Aggrecan aggregates bind very strongly to water.
2) The proteoglycans are trapped within the fibrilar complex of collagen.
3) Entrapment keeps the collagen fibrils under tension.
4) Maintains high osmotic pressure within the cartilage tissue.
What are the three small leucine-rich proteoglycans found in articular cartilage?
What is decorin? What is its structure and function?
• A small leucine-rich proteoglycan.
• Formed of a single chain of chondroitin sulphate or dermatan sulphate.
• Found in the lacunae, binds growth factor near cell surface receptors.
What is biglycan? What is its structure and function?
• A small leucine-rich proteoglycan found in articular cartilage.
• Composed of two chondroitin sulphate or dermatan sulphate chains.
• Binds to collagen fibres to regulate their size, also binds to some growth factors and sequesters them in the ECM.
What is fibromodulin? What is its structure and function?
• It is a small leucine-rich proteoglycan found in articular cartilage.
• It is formed of 3-5 keratan sulphate chains.
• Binds to collagen fibrils and regulate fibrillogenesis.
In articular cartilage is the tide mark present in adult or immature cartilage? And what effect does this have?
The presence of the tidemark restricts chondrocyte access to nutrition from the subchondral bone vasculature.
Where does the majority of nutrition for adult articular cartilage come from?
Diffusion from the synovial fluid.
What are 5 biochemical changes that occur in cartilage due to ageing?
1) Cell metabolism slows down and cell numbers decrease.
2) Collagens and other proteins become cross-linked.
3) Type IX collagen synthesis is reduced.
4) Biochemical changes in aggrecan.
5) Degradation products of cartilage matrix accumulate.
How are cartilage collagens cross-linked with ageing?
• The modification of hydroxylysine residues in the collagen chains.
• Forms pyridinoline cross-links.
What are some of the biological changes that occur in aggrecan with ageing?
• Shorting of the Chondroitin Sulphate chains.
• Lengthening of the Keratan Sulphate chains.
What performs the degradation of matrix components in cartilage turnover?
- Matrix Metalloproteinase (MMPs)
- Aggrecanases (ADAMTS 4&5)
What are required by 'metalloproteinases' to perform their function and what is their function?
• Zinc and/or Calcium
• They breakdown the cartilage matrix in articular cartilage turnover.
What are the major types of Matrix Metalloproteinases (MMPs) found in cartilage metabolism?
• Membrane-bound MMPs
How do aggrecanases help to break down cartilage matrixes?
• They specifically cleave the bond between glutamate and alanine in the interglobular domain of aggrecan.
• This causes the glycosaminoglycan attachment domains of the aggrecan to break off from the collagen matrix.
What is the mechanism of Rheumatoid Arthritis in the degredation of joint space?
• Deposition of immune complexes in the joint space, this causes an influc of inflammatory cells which secrete cytokines which induce cartilage degradation.
How does osteoarthritis cause joint pain/dysfunction?
• Proteoglycan breakdown leads to the loss of the cartilage collagen mesh.
• Compromises mechanical structure of the joint.
What are the four main functions of skeletal tissue?
- Haematopoetic red marrow
- Energy - Lipid-filled yellow marrow
What are the four characteristic bone types? Give an example for each.
• Long bone - Humerus
• Short bones - Carpals
• Flat Bone - Parietal bone
• Irregular bone - Vertebra
What are the three parts of a long bone?
• Proximal epiphysis
• Distal epiphysis
What is cortical bone and what are it's properties?
• 'Compact bone'
• Low turnover.
• Mainly protective and mechanical function.
• Composed of concentric layers of dense connective tissue.
Corticol bone: What are lamellae?
These are the layers of connective tissue that make up the bone.
- Circumfrential lamellae surround the entire bone.
- There is also lamellae that make up the osteons.
Corticol bone: What is the name of the main canals through which vasculature pass?
Haversian Canals, these are interconnected by perforating canals (Volkmann's canals).
Corticol bone: What are Volkmann's canals?
These are perforating canals that interlink the Haversian canals.
Corticol bone: What are the names of the holes in which osteocytes reside? What is the name of the passages that connect them?
What is the composition of bone extracellular matrix?
- 95% collagen (Mostly type I)
- 5% Proteoglycans and non-collagenous protein
What is scurvy, what is it's effect on bone?
• Dietary deficiency of vitamin C.
• Collagen chains fail to form triple-helix structure, leading blood vessels, bone, skin, tendons to become fragile.
What is osteogenesis imperfecta?
• Mutation in type I collagen, leading to weak bones which easily fracture.
What is Ehlers-Danos syndrome?
• Mutations in type III collagen, leads to fragile skin, weak vessels and hypermobility.
What are chondrodysplasias?
• Mutation in type II collagen.
• Leads to abnormal cartilage, bone and joint deformities.
What secretes proteoglycans for bone formation?
What is an unmineralised bone know as?
What are the four types of bone cells and what are their functions?
1) Osteoprogenitor cells- precursor cells that differentiate into bone forming cells.
2) Osteoblasts - bone-forming cells that deposit osteoid and control mineralisation.
3) Osteocytes - Modified osteoblasts that become surrounded by newly formed bone.
4) Osteoclasts - Macrophage-type cells that absorb bone during the remodelling process.
Where are osteocyte bodies and where are their processes?
• Bodies - Lacuna
• Processes - Canalculi
Where are osteoclasts located?
On the surface of the bone in small hollows called Howship's Lacunae that are formed from lysomalase that the osteoclasts secrete that digest bone.