Mechanisms of bone loss

Question 1

Why is the area of the gingival cuff important?

Answer 1

It is critical in maintaining the correct relationship between the gingival and the tooth thereby protecting the deeper tissues of the PDL and alveolar bone

Question 2

Name the main cells found in the gingival cuff

Answer 2

1. Osteoclasts
2. Osteoblasts
3. Fibroblasts
4. Macrophages

Question 3

What do osteoclasts do?

Answer 3

They are bone resorbing cells

Question 4

What are the characteristics of osteoclasts?

Answer 4

They are very large and multinucleate

They have a brush border when adjacent to the bone surface where active resorption is occurring

Question 5

Where are osteoclasts situated?

Answer 5

They are situated in resorption pits called Howship’s lacunae

Question 6

What do osteoblasts do?

Answer 6

They are bone forming cells

Question 7

What are the characteristics of osteoblasts?

Answer 7

They are characteristically found as a single cell layer lining the bone surface
They are active protein producing cells

Question 8

What do fibroblasts do?

Answer 8

They are responsible for forming and painting the collagenous matrix of the ligament and marina prop

Question 9

Describe the fibroblasts

Answer 9

They are very active cells

Question 10

Why are fibroblasts active cells?

Answer 10

As they have a rapid turnover time for their matrix in the PDL tissues

Question 11

What is the origin of the macrophages?

Answer 11

They are of monocyte lineage

Question 12

Name the process by which collagen is degraded

Answer 12

Phagocytosis

Question 13

What does the secretion and degradation of collagen have to be in synchrony?

Answer 13

So that the overall level of matrix is constant

Question 14

How are osteoclasts formed?

Answer 14

Under the control of a growth factor called RANKL, monocytes fuse and form osteoclasts

Question 15

Where does the growth factor RANKL originate from?

Answer 15

Adjacent osteoblasts

Question 16

Describe where RANKL is found in a cell

Answer 16

RANKL may be free within the matrix or bound to the osteoblast cell membrane

Question 17

What does RANKL bind to?

Answer 17

It binds to a specific receptor on the monocytes

Question 18

How does the osteoblast control the rate of osteoclast formation?

Answer 18

By modulating the production of RANKL

Question 19

What happens once the osteoclasts fully differentiated?

Answer 19

It starts to degrade bone

Question 20

How do osteoclasts degrade bone?

Answer 20

They pump protons into the adjacent bone to dissolve minerals and then potent enzymes, mainly Cathepsin K, to breakdown the bone matrix.

Question 21

Which enzyme is mainly released to break down bone?

Answer 21

Cathepsin K

Question 22

Which growth factor helps regulate the formation of osteoclast?

Answer 22

RANKL

Question 23

What is the modulation of RANKL production influenced by?

Answer 23

Influenced by the applied loading on the bone (either directly by the osteocytes and osteoblasts detecting the mechanical stresses within the bone itself)
OR
Indirectly via macrophages

Question 24

What do macrophages reason to that can help modulate the production of RANKL?

Answer 24

They respond to loading by the production of cytokines such as interleukin-1 (IL-1).

Question 25

The action of what increase the production of RANKL by osteoblasts?

Answer 25

By the action of IL-1

Question 26

What is maintenance of the alveolar bone dependent on?

Answer 26

On sufficient load derived fro the presence of functioning teeth

Question 27

What happens to the alveolar bone if teeth are lost?

Answer 27

The alveolar bone will be resorbed as the balance is upset and bone degradation outstrips formation.

Question 28

What situation can tip the balance between formation and destruction more towards reposition?

Answer 28

can also be tipped in the direction of bone resorption by the intervention of certain exogenous plaque bacterial- derived material e.g lipo-polysaccharide (LPS) and bacterial enzymes which directly or indirectly affect the cells and matrix in the gingival cuff region.

Question 29

What situation can tip the balance between formation and destruction more towards destruction??

Answer 29

Losing teeth or having them extracted

Question 30

What is the colloquial name for the periodontal disease a lot of sheep suffer from?

Answer 30

Broken mouth

Question 31

What happens if we add a bacterial plaque adjacent to the epithelium in the PDL?

Answer 31

LPS derived from this plaque will pass through the epithelium and interact with the cell populations in the connective tissue and on the bone surface.

Question 32

On what cell does LPS have the greatest effect?

Answer 32

Macrophages

Question 33

What effect can LPS have on osteoblasts?

Answer 33

to up regulate RANKL production

Question 34

What effect can LPS have on monocytes?

Answer 34

To accelerate their fusion to osteoclasts

Question 35

What effect can LPS have in macrophages?

Answer 35

stimulates an increase IL-1 production

Question 36

Name some targets for IL-1

Answer 36

1. Osteoblasts | 2. Fibroblasts

Question 37

How does an increase in IL-1 affect the osteoblasts?

Answer 37

RANKL production is upregulated which in turn leads to further recruitment of monocytes and the formation of more osteoclasts

Question 38

How does an increase in IL-1 affect the Fibroblasts?

Answer 38

Triggered to produce their own IL-1,some of which again acts upon the osteoblast population and some acts in a paracrine fashion to stimulate yet more IL-1 from neighbouring cells. The IL-1 also stimulates the fibroblasts to produce extracellular collagenases Also stimulates the fibroblasts to produce another cytokine, interleukin 6 (IL-6).

Question 39

What does interleukin 6 (IL-6). do?

Answer 39

This cytokine increases the effectiveness of RANKL in stimulating osteoclast formation.

Question 40

How does an increase in IL-1 affect the osteoclasts?

Answer 40

Can upregulate cathepsin K production and thereby increase the effectiveness of individual cells in degrading the bone matrix

Question 41

Summarise the actions of LPS produced from bacteria

Answer 41

1. Acts on osteoblasts to up regulate RANKL production 2. Acts on monocytes o increase osteoclast formation 3, Acts on macrophages to up regulate IL-1 production

Question 42

Summarise the actions of IL-1 produced from bacteria

Answer 42

1. Acts on osteoblasts to up regulate RANKL production 2, Act on fibroblasts to up regulate IL-1 production 3. Acts on fibroblasts to to up regulate IL-6 production 4. Act on fibroblasts to induce collagenase production

Question 43

What effect does the presence of bacteria have on alveolar bone?

Answer 43

Leads to alveolar bone loss

Question 44

How does the presence of bacteria lead to alveolar bone loss?

Answer 44

1. Direct stimulation of osteoclast formation 2. The production of an inflammatory response including the production of numerous cytokines which directly or indirectly increased osteoclast formation and activity 3. A loss of loading on the bone which can itself result in further bone loss