Bone And Joint 1 - The Joint And Its Connective Tissue

Front 1

What are the functions of joints?

Back 1

1. Give skeleton mobility

2. Hold skeleton together

Front 2

What are the classifications of bone?

Back 2

1. Fibrous

2. Cartilagenous

3. Synovial

Front 3

What structural components do all synovial joint have in common?

Back 3

1. Articular Cartilage

2. Joint Cavity

3. Articular Capsule

4. Synovial Fluid

5. Reinforcing Ligaments

Front 4

Label:

Back 4

1. Muscle

2. Synovium

3. Synovial Fluid

4. Cartilage

5. Tendon

6. Tendon sheath lined by synovium

7. Capsule (ligaments)

8. Bone

Front 5

What is the role of:

1. Ligaments

2. Cartilage

Back 5

1. Ligaments stabilise the joint

2. Cartilage cushions the joint

Front 6

Label:

Back 6

1. Femur

2. Tibial collateral ligament

3. Medial meniscus

4. Anterior cruciate ligament

5. Tibia

6. Fibula

7. Lateral meniscus

8. Posterior cruciate ligament

9. Fibular collateral ligament

10. Patella

Front 7

How does joint tissue composition vary between connective tissues?

Back 7

Vary based on function:

1. Tendon / Ligament : Dense, fibrous, strong in tension, transmits force

2. Cartilage: Resists compression - hydrated meshwork

3. Bone: Provides support and protection - Rigid Mineralised sheets.

Front 8

What is the cellular composition of connective tissues?

What types of cells exist?

What does each type synthesise?

Back 8

All joint tissues are mainly extracellular matrix. The cells which do exist, do so as they synthesise extracellular matrix:

1. Fibroblasts - Synovium, tendon etc

2. Chondrocytes - Cartilage

3. Osteocytes - Bone

4. Stem cells - New ECM synthesising cells

Front 9

What are the main varieties of molecules which make up the extracellular matrix of connective tissue?

Back 9

1. Collagens

2. Proteoglycans

3. Glycoproteins

Front 10

What are proteoglycans important for?

Give 2 examples.

Back 10

Important for connective tissue material properties - hold water in tissues and thus convey vasoelasticity.

Also important for interactions with cells, cytokines and collagen.

Aggrecan, Decorin.

Front 11

1. What molecule types are 'Biolubricants'?

2. What are they important for?

3. Give 3 examples of biolubricants.

Back 11

1. Glycosaminoglycans and Proteoglycans

2. Essential for lubricating joint function

3. i) Hyduronan

ii) lubrican / Proteoglycan 4

ii) Aggrecan

Front 12

What are bursae?

Back 12

Bursae are small synovial fluid filled sacs which are lined with synovium. They are found in and around most synovial joints.

Front 13

What is the function of bursae?

Back 13

Bursae function to facilitate movement.

Front 14

What is the pathology which affects the bursae?

Back 14

Bursitis - inflammation of the bursae.

Front 15

What are the two types of synovial cells?

What are the functions of each?

Back 15

Type A (macrophage like) synovial cells - phagocytic immune function

Type B (Fibroblast like) produce synovial fluid.

Front 16

What is the role of synovial fluid?

Back 16

Lubricates the joints.

Front 17

What is the main structural component of connective tissue?

Back 17

Collagen.

Front 18

Describe the tertiary structure of collagen.

Back 18

1. 3 alpha chains (each a single gene product) are arranged in a triple helix.

Front 19

What is a crucial feature of the primary sequence?

Back 19

Glycine every 3 residues

Front 20

What is the hallmark structural motif of collagen?

Back 20

Gly - X - Y

Where:

X = Usually a proline

Y = Usually a hydroxyproline

Front 21

What are the major structural collagens?

Back 21

Types I, II and III

Front 22

What is the first stage of collagen synthesis?

Back 22

Synthesised as an inactive procollagen molecule in the cell and then exocytosed into the ECM

Front 23

How is procollagen activated?

Back 23

N + C terminals cleaved by pro collagen peptides

Front 24

What is the extracellular matrix molecule compositions of:

1. Bone

2. Cartilage

3. Tendon / Ligaments

Back 24

1. 90% Type I collagen, 5% Type V collagen - arranged in sheets which are mineralised

2. 90% Type II collagen, 10% aggrecans - arranged in a meshwork

3. 90-95% type I collagen, 5% type II collagen, 0.5% DSPG - arranged in parallel fibres.

Front 25

What is the key determinant of tendon tensile strength?

Back 25

The Parallel type I collagen fibril bundles.

Front 26

How is constant fluid flow in tendon fibril bundles ensured?

What is the effect of this process?

Back 26

The ebb and flow of proteoglycan swelling. Collagen resists the swelling and thus acts like a pump which forces fluid through the tendon.

Allows renewal of nutrition for chondrocytes, removal of waste products and thus synthetic activity.

Front 27

How is extracellular matrix turnover in connective tissues mediated?

Back 27

Mediated through the secretion of secreted proteases.

Front 28

What are the key secreted proteases?

Back 28

1. MMPs - Matrixmetalloproteinases

2. ADAMTs (A disintegrin and metalloproteinase with thrombospondin motifs)

Front 29

How many MMPs are there?

What are the important MMPs which act as collagenases?

Back 29

23 in total

1, 2, 8, 13, 14

Front 30

How many ADAMTs are there?

How is their activity regulated?

Back 30

19 in total

Inhibited by TIMP-3

Front 31

What are the different types of MMP?

Back 31

1. Archetypal -

i) Collegenases

ii) Stromelysins

2. Gelatinase

3. Furin Activated

4. Matrilysins

Front 32

What are the different types of ADAMTs?

Back 32

1. Angioinhibitory

2. Pro collagen N-Peptidase (cleaves the N terminal of procollagen)

Front 33

How is the activity and function of an MMP regulated throughout its life cycle?

Back 33

1. Before formation - translation / transcription

2. Produced in inactive form

3. Activation of zymogen

4. Inhibition when acting on target ECM component

Front 34

How is the secretion of MMPs controlled?

Back 34

a) transcriptionally controlled - cytokines, growth factors, mechanical load

b) IL-1

c) Tumour necrosis factor

Front 35

How are MMP zymogens activated?

Back 35

1. By other MMPs

2. Other enzymes

Front 36

How are active MMP's regulated?

Back 36

By TIMPs which bind with MMPs to produce an inactive complex.

Also by alpha 2 macroglobulin

Front 37

What does TIMP stand for?

Back 37

Tissue Inhibitor of Metallo Proteinases

Front 38

What diseases are associated with altered ECM turnover?

Back 38

1. Osteoarthiritis - degeneration of cartilage / bone - increased matrix degradation

2. Rheumatoid arthiritis - increased matrix degradation & reduced synthesis - systemic

3. Tendinopathy - Increased matrix degradation and synthesis

Front 39

What will SEVERE osteoarthiritis result in?

Back 39

Severe OA will result in a loss of proteoglycan and collagen fibrillation.