What is it in articular cartilage that give the tissue it's elastic properties?
The osmotic pressure of the GAGs
What mutation causes osteogenesis imperfecta, and what are the symptoms?
Mutation in Type I collagen
Leads to weak bones that fracture easily.
What is the function of the gelatinases (MMP-2 & -9)?
The breakdown denatured collagens (triple helix already disrupted).
What ions must be present in order for the MMP and ADAMTS-4 & -5 to degrade articular cartilage?
What are the characteristics of cortical bone?
- Haversian canals
- Volkmann's canals
- Concentric lamellae
- Haversian systems
- Interstitial lamellae
What causes Ehlers-Danlos syndrome and what are the symptoms?
A mutation in Type III collagen
- Fragile skin
- Fragile blood vessels
- Hypermobile joints
Which amino acid are involved in covalently binding GAGs to a protein core?
- Serine - hydroxyl group
- Threonine - hydroxyl group
- Asparagine - amine group
What matrix glycoproteins are found in articular cartilage?
- Cartilage oligomeric matrix protein (COMP)
- Cartilage matrix proteins (CMPs)
When can a reverse Hill-Sachs lesion occur?
Repeated posterior dislocation of the shoulder.
What diseases are characterised by the failure of the osteoid to calcify?
- Rickets - Children
- Osteomalacia - Adults.
What are the small hollows on bone, where osteoclasts are degrading bone, called?
What is the function of RANKL in bone?
It increases resorption as it stimulates the production of mature osteoclasts, and also activates already mature osteoclasts.
What are the 4 main parts of a synovial joint?
- Articular cartilage
- Synovial fluid
- Joint capsule
What are the 6 morphological zones of articular cartilage?
- Superficial zone
- Mid zone
- Deep zone
- Calcified zone
Which constituent of articular cartilage has the longest half-life?
Collagen - measured in years.
How common is a Bankart lesion in an anterior shoulder dislocation?
It occurs in ~85% of anterior dislocations
What are the 4 stages of ostesoarthritis?
- Early stage - superficial loss of proteoglycan
- Intermediate stage - proteoglycan loss compromises collagen framework
Late stage - chondrocyte clusters form.
Which part of the bone, trabecular or cortical, has the greatest rate of turnover and remodelling?
What small proteoglycans are found in the ECM of articular cartilage and what is their function?
- Biglycan - binds growth factors close to chondrocyte surface
- Decorin - regulates collagen fibril size by binding to them
- Fibromodulin - Controls fibrillogenesis.
What are Benninghoff arcades?
They are where the collagen fibres are arranged in an arch formation, with chondrocytes sitting in lacunae between the fibres.
What are the 2 main GAGs that are bound to aggrecan, and which is more abundant?
- Chondroitin sulphate (65%)
- Keratin sulphate (35%)
What position is the arm most likely to dislocate and why?
When the arm is abducted to 90 degrees and externally rotated
This is because the only support structure is the weak inferior glenohumeral ligament
What feature of GAGs means that bind water very well?
They are polyanionic (large negative charge) which attacts water towards them.
What is the major collagen type in cartilage and what is its main function?
Type II collagen; To provide tensile strength.
How can you confirm a posterior dislocation?
What is a Hill-Sachs lesion?
It is a cortical depression in the posterolateral part of the humerus head
What are the 3 stages of bone development?
Osteoid - Collagen present but no mineralisation
Woven bone - Randomly arranged collagen with crystals present outside the fibres
Lamellar bone - Well-organised collagen with crystals present within the fibres.
What direction are most shoulder dislocations?
Anteriorly - the head of the humerus moves anteriorly to the glenoid cavity.
How doess articular cartilage in a young person differ from that found in adults?
- It is very cellular
- It has little matrix
- There is no zonal morphology
- There is no tidemark
What are some symptoms of Paget's disease of bone?
- Bone pain and increased thickness
- Deafness and craniofacial complications
- Headaches and neurological complications including visual
- Deformities and osteosarcoma.
What is the function of the Stromelysins (MMP-3, -8, & -10)?
To degrade the non-collagenous matrix proteins, but not aggrecan.
What is fibrodysplasia ossificans progressiva?
It is the inappropriate mineralisation of soft tissues in the body, leading to excess bone
It can occur spontaneously or after trauma
Autosomal dominant condition
What causes chondrodysplasias, and what are the symptoms?
Mutation in Type II collagen
- Abnormal cartilage
- Bone and joint deformities.
What are the characteristics of adult articular cartilage?
- No lymphatics
- No basement membrane
What is the organic matrix of bone made up of?
- Type I collagen (95%)
- Proteoglycans and non-collagenous proteins (5%) - BMP, osteopontin, osteonectin and osteocalcin.
What are the functions of bone?
- Aid in movement
- Mineral storage
- Storage of haemopoietic red marrow
- Storage of lipid filled yellow marrow - energy
What is the enzyme that cross links the matrix molecules such as matrilins and CMP?
Which residues on matrix proteins are involved in the cross-linkage of these matrix proteins by transglutaminase?
How does cartilage change as a person gets towards old age?
- There are fewer cells that also have a lower metabolism
- There are cross-links between the collagens and other matrix molecules
- Reduced Type IX collagen synthesis
- CS chains are shorter on aggrecan
- Degradation products build up.
Where do aggrecanases break aggrecan?
Between an glutamate and alanine residue in the interglobular domain.
What lies in the canaliculi of bone and what do they allow?
Dendritic processes that allow communication between osteocytes via gap junctions.
What is the main component of the inorganic part of bone extracellular matrix?
Calcium hydroxyapatite crystals
What does a mutation in the COMP cause?
What is a Bankart lesion?
It is an injury to the anterior glenoid labrum due to repeated dislocation
What molecule does aggrecan bind to, to form large aggregations?
What is the function of Vitamin C (Ascorbic acid) in the body?
It is an essential cofactor for the hydroxylases that convert proline and lysine into hydroxyproline and hydroxylysine, which stabilise the collagen within body, giving it its strength.
Where is trabecular bone found?
In the end of long bones and axial skeleton
What are the 4 types of bone cell and what does each 1 do?
Osteoprogenitor cells - Precursor cells that are able to self-replicate and differeniate
Osteoblasts - Bone forming cells
Osteocytes - Modified osteoblasts that act as sensors in the bone
Osteoclasts - Marcophage-like cells that resorb bone
What effects do PTH and Vit D3 have on bone?
The increase the rate of resorption.
What are the 4 broad categories of osteoporosis?
Postmenopausal - BF increased, but BR increases more
Senile - BF decreases and BR increases
Glucocorticoid induced - BF decreases and either no change or increased BR
Disuse - BF decreased and BR increased.
When is posterior dislocation likely to occur?
- Electric shock
- Fall with arm adducted and internally rotated
What is the repeating disaccharide unit made up of in GAGs?
- A hexuronic acid or galactose
Apart from Type II collagen, what other types of collagen are found in articular cartilage, and what do they do?
- Type XI (3%); Hold microfibrils together to form fibrils (5 microfibrils)
- Type IX (2%); Anchor fibrils to other matrix components to resist shear forces
- Type IV (1%); Form fine fibrils in the lacunae around cells
What is the function of the collagenases (MMP-1 & -13)?
To degrade triple helical collagen
How do chondrocytes in articular cartilage get their nutrients and get rid of their waste products?
Nutrients diffuse from blood vessels into the synovial capsule and fluid.
The loading and then unloading of cartilage draws the nutrients from the fluid into the cartilage.The opposite happens for the waste products.
Which residue of collagen is modified in the formation of pyridinoline cross-links?
What is the major proteoglycan of articular cartilage?
When is a Hill-Sachs lesion likely to occur?
It occurs when there is repeated anterior dislocation of the shoulder.
What are the cavities that osteocytes lie in?