FOM 3.1.3

Question 1

What are is this, what is it stained with and what are the arrows pointing at?

Answer 1

This is hyaline cartilage stained with H and E. The arrows are pointing at chondrocytes in their lacunae.

Question 2

How does hyaline cartilage accomplish its role as a shock absorber?

Answer 2

Hyaline cartilage functions like a shock absorber or biomechanical spring: solvation water is bound water which interacts with the negatively charged proteoglycans and is squeezed out of cartilage on compression and returns and binds during decompression.

Question 3

What is the rigidity of the hyaline cartilage dependent on?

Answer 3

Rigidity is dependent on the electrostatic interactions between type II collagen fibrils and the GAGs comprising the proteoglycans resulting in a cross-linked matrix.

Question 4

What is responsible for rigidity of cartilage?

Answer 4

Type II collagen binding to the proteoglycan aggregate

Question 5

How is the protein portion of the GAG synthesized and processed?

Answer 5

It is synthesized in the ER and sugars are added to it in the golgi

Question 6

What is a main differenct between cartilage and bone andhow does this affect the way nutrients are delivered to it?

Answer 6

Cartilage lacks blood vessels, it is AVASCULAR which requires that nutrients and waste seep through the matrix by diffusion.

Question 7

Deposition of lime salts in the form of hydroxyapatite crystals does what for bone?

Answer 7

It prevents the diffusion of metabolites and prevents interstitial growth, both of these occur in the cartilage

Question 8

What is are the two types of bone?

Answer 8

Compact bone: dense without cavities

Cancellous (trabecular) bone: 3-dimensional lattice of branching bony spicules, forming trabeculae around marrow spaces

Question 9

What are the arrows in this picture pointing to?

Answer 9

The top arrows are pointing to cancellous bone and the bottom arrows are pointing to compact bone

Question 10

What does each of the numbers correspond to?

Answer 10

1. Compact bone
2. Periosteum
3. Marrow cavities
4. Trabecular bone
5. Epiphysis
6. Metaphysis
7. Diaphysis

Question 11

What is the composition of the bone matrix?

Answer 11

Organic Matrix 35% - consisting of 85-90% type I collagen, proteins, glycoproteins

Inorganic Salts - Hydroxyapatite crystals

Question 12

What is an osteoprogenitor cell and what is its role?

Answer 12

Pluripotent stem cell from mesenchyme. Capable of differentiating into osteogenic cells, osteoblasts. Found in the periosteum and endosteum as bone lining cells in non-growing regions and differentiate into osteoblast following a fracture

Question 13

What are osteoblasts and what are their role?

Answer 13

These cells synthesize and secrete organic matrix of the bone: types I collagen, non-collagenous protein and alkaline phosphatase.

Question 14

What are osteocytes?

Answer 14

Osteoblasts that have trapped themselves in calcified matrix

Question 15

What is an osteoclast?

Answer 15

These are giant multinucleated cells that are derived from monocytes. Produce an acidic environment ideal for the dissolution of bone matrix. These are also said to have a ruffled border

Question 16

What is the fate of mesenchyme cells in bone?

Answer 16

These become osteoprogenitor cells that develope into osteoblasts and the osteocytes. Also bone lining cells

Question 17

What is the fate of bone marrow monocyte precursors?

Answer 17

These form monocytes that will form osteoclasts

Question 18

What is RANK-L?

Answer 18

RANK-L is synthesized by osteoblasts and it is a receptor that stimulates osteoclastogenesis

Question 19

What is osteoprotegerin?

Answer 19

This is a decoy receptor for RANK-L

Question 20

What is osteoid and how is it used?

Answer 20

Osteoid is type I collagen and proteoglycans, this is all synthesized by osteoblasts.

Question 21

What are the main characteristics of an osteoclast?

Answer 21

The ruffled border

The bone matrix

The tight seal

Multiple nuclei

High amounts of lysosomes

Question 22

What is the periosteum?

Answer 22

Dense connective tissue with osteogenic potential that surrounds the bone. This means there is osteoprogenitor cells comprising the bone lining the outside

Question 23

What is the endosteum?

Answer 23

It is found lining the marrow cavity and has osteogenic potential. Means there are osteoprogenitor cells that line the inside

Question 24

What are each of the arrows pointing at?

Answer 24

Blacks lines - bone matrix

Blue arrows - osteocytes

Yellow - Skeletal muscle

Darker green line- periosteum the inner layer is the osteopregenitor cells

Lime green - osteoblasts on the surface of the bone

Question 25

What is the ARF cycle?

Answer 25

Question 26

What is the effect of PTH on bone?

Answer 26

Parathyroid hormone produced by the parathyroid gland and functions to increase serum Ca++ levels through several mechanisms shown in the figure. In bone, PTH increases the number of osteoclasts and the ruffled border activity of existing osteoclasts

Question 27

What is the action of PTH on osteoclasts and osteoblasts?

Answer 27

Osteoblast are exposed to PTH - first effect is to release MCSF leads to increase differentiation of osteocytes from monocyte precursor

Osteoblast then release RANK-L which binds to RANK on osteoclast- binding to osteoclast stimulates ruffled border activity.

Question 28

Where would you want a drug to target for a disease like osteoperosis where the osteoclasts are winning?

Answer 28

You would want it to target RANK-L

Question 29

What is osteoprotegerin?

Answer 29

increase removes RANK-L and counteracting the action of the osteoclasts

Question 30

What are the roles of bisphosphonates?

Answer 30

kill osteoclasts by inducing apoptosis in osteoclasts

Also have a role in inhibiting osteoclast aggregation

Question 31

What would be another ideal target for treatment of osteoperosis?

Answer 31

Increased expression of osteoprotegerin by osteoblasts

Question 32

What is M-CSF and what does increasing it do?

Answer 32

Increasing M-CSF increases the number of osteoclasts and increase the activity of osteoclasts

Question 33

What is the purspose of chondronectin?

Answer 33

Chondronectin promotes adherence of chondrocytes to the matrix

Question 34

What is the purpose of osteocalcin?

Answer 34

Required for mineralization

Question 35

The molecular basis for shock absorption within articular cartilage is what?

Answer 35

Hydration of glycosaminoglycans