Mechanisms of bone loss Flashcards
Why is the area of the gingival cuff important?
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
Name the main cells found in the gingival cuff
- Osteoclasts
- Osteoblasts
- Fibroblasts
- Macrophages
What do osteoclasts do?
They are bone resorbing cells
What are the characteristics of osteoclasts?
They are very large and multinucleate
They have a brush border when adjacent to the bone surface where active resorption is occurring
Where are osteoclasts situated?
They are situated in resorption pits called Howship’s lacunae
What do osteoblasts do?
They are bone forming cells
What are the characteristics of osteoblasts?
They are characteristically found as a single cell layer lining the bone surface
They are active protein producing cells
What do fibroblasts do?
They are responsible for forming and painting the collagenous matrix of the ligament and marina prop
Describe the fibroblasts
They are very active cells
Why are fibroblasts active cells?
As they have a rapid turnover time for their matrix in the PDL tissues
What is the origin of the macrophages?
They are of monocyte lineage
Name the process by which collagen is degraded
Phagocytosis
What does the secretion and degradation of collagen have to be in synchrony?
So that the overall level of matrix is constant
How are osteoclasts formed?
Under the control of a growth factor called RANKL, monocytes fuse and form osteoclasts
Where does the growth factor RANKL originate from?
Adjacent osteoblasts
Describe where RANKL is found in a cell
RANKL may be free within the matrix or bound to the osteoblast cell membrane
What does RANKL bind to?
It binds to a specific receptor on the monocytes
How does the osteoblast control the rate of osteoclast formation?
By modulating the production of RANKL
What happens once the osteoclasts fully differentiated?
It starts to degrade bone
How do osteoclasts degrade bone?
They pump protons into the adjacent bone to dissolve minerals and then potent enzymes, mainly Cathepsin K, to breakdown the bone matrix.
Which enzyme is mainly released to break down bone?
Cathepsin K
Which growth factor helps regulate the formation of osteoclast?
RANKL
What is the modulation of RANKL production influenced by?
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
What do macrophages reason to that can help modulate the production of RANKL?
They respond to loading by the production of cytokines such as interleukin-1 (IL-1).
The action of what increase the production of RANKL by osteoblasts?
By the action of IL-1
What is maintenance of the alveolar bone dependent on?
On sufficient load derived fro the presence of functioning teeth
What happens to the alveolar bone if teeth are lost?
The alveolar bone will be resorbed as the balance is upset and bone degradation outstrips formation.
What situation can tip the balance between formation and destruction more towards reposition?
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.
What situation can tip the balance between formation and destruction more towards destruction??
Losing teeth or having them extracted
What is the colloquial name for the periodontal disease a lot of sheep suffer from?
Broken mouth
What happens if we add a bacterial plaque adjacent to the epithelium in the PDL?
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.
On what cell does LPS have the greatest effect?
Macrophages
What effect can LPS have on osteoblasts?
to up regulate RANKL production
What effect can LPS have on monocytes?
To accelerate their fusion to osteoclasts
What effect can LPS have in macrophages?
stimulates an increase IL-1 production
Name some targets for IL-1
- Osteoblasts
2. Fibroblasts
How does an increase in IL-1 affect the osteoblasts?
RANKL production is upregulated which in turn leads to further recruitment of monocytes and the formation of more osteoclasts
How does an increase in IL-1 affect the Fibroblasts?
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).
What does interleukin 6 (IL-6). do?
This cytokine increases the effectiveness of RANKL in stimulating osteoclast formation.
How does an increase in IL-1 affect the osteoclasts?
Can upregulate cathepsin K production and thereby increase the effectiveness of individual cells in degrading the bone matrix
Summarise the actions of LPS produced from bacteria
- Acts on osteoblasts to up regulate RANKL production
- Acts on monocytes o increase osteoclast formation
3, Acts on macrophages to up regulate IL-1 production
Summarise the actions of IL-1 produced from bacteria
- Acts on osteoblasts to up regulate RANKL production
2, Act on fibroblasts to up regulate IL-1 production - Acts on fibroblasts to to up regulate IL-6 production
- Act on fibroblasts to induce collagenase production
What effect does the presence of bacteria have on alveolar bone?
Leads to alveolar bone loss
How does the presence of bacteria lead to alveolar bone loss?
- Direct stimulation of osteoclast formation
- The production of an inflammatory response including the production of numerous cytokines which directly or indirectly increased osteoclast formation and activity
- A loss of loading on the bone which can itself result in further bone loss
