Oddr E Lec Mechanism Of Bone Loss

Front 1

The area of gingival cuff is critical in doing what

There are a number of what in this region

What do they do

Back 1

The area of the gingival cuff is critical in maintaining
the correct relationship between the gingiva and the
tooth, thereby protecting the deeper tissues of the
periodontal ligament and alveolar bone. There are a
number of cell types in this region which, in normal
healthy conditions, act together in a coordinated
fashion to maintain the status quo in terms of
connective tissue and alveolar bone integrity.

Front 2

Cells usually involved in the bone loss process

Explain their appearance and presence

Back 2

The major cells involved in this ‘homeostatic’ process
are: the osteoclast – the bone resorbing cell which is
characteristically very large and multinucleated and
has a brush border adjacent to the bone surface
where active resorption is taking place. The
osteoclasts are usually situated in resorption pits
called Howship’s lacunae.

Front 3

What is the osteoblast

What are the periodontal and and gingival fibroblasts

Back 3

The osteoblast – the bone
forming cell which is characteristically found as a
single cell layer lining the bone surface. It is an active
protein producing cell.

The periodontal and gingival
fibroblast – the cell responsible for forming and
maintaining the collagenous matrix of the ligament
and lamina propria

Front 4

What is the osteoblast

What are the periodontal and and gingival fibroblasts

Back 4

The osteoblast – the bone
forming cell which is characteristically found as a
single cell layer lining the bone surface. It is an active
protein producing cell.

The periodontal and gingival
fibroblast – the cell responsible for forming and
maintaining the collagenous matrix of the ligament
and lamina propria

Front 5

Why is the cell very active

Back 5

It is a very active cell as the turnover time for the matrix in periodontal tissues is rapid.

Front 6

What is a macrophage

Back 6

The macrophage – a cell of the monocyte
lineage which an active member of the tissue’s
defensive armoury.

Front 7

The connective tissue of the periodontium is very cellular so what does this mean

Back 7

The connectivetissue of the periodontium is very cellular so there arelots of these cells which are turning over the matrix very rapidly with high rates of collagen production
and degradation, the latter by a process of
phagocytosis of individual fibril fragments.

Front 8

What 2 processes work together and why

Back 8

lots of these cells which are turning over the matrix
very rapidly with high rates of collagen production
and degradation, the latter by a process of
phagocytosis of individual fibril fragments. These two
processes are basically in synchrony so that the
overall level of matrix is constant

Front 9

The tissue is also highly ....

From which.....

Back 9

This tissue is also highly vascularised from which circulating monocytes are recruited

Front 10

Under the control of a particular growth factor ( name it ) what happens

Where does this growth factor originate
What does it do

Back 10

Under the control of a growth factor
called RANKL, originating from adjacent osteoblasts,
they fuse and form osteoclasts.

RANKL may be free within the matrix or bound to the osteoblast cell membrane and it binds to a specific receptor on th emonocyte membrane

Front 11

By modulating the production of RANKL what happens

Once the osteolcalst is fully differentiated what does it do

Back 11

By modulating the production
of RANKL the osteoblast controls the rate of
osteoclast formation. Once the osteoclast is fully
differentiated it degrades bone by first pumping
protons into the adjacent bone to dissolve mineral
and then potent enzymes, mainly Cathepsin K, to
breakdown the bone matrix.

Front 12

Bone however does what

Back 12

Bone, however, is a dynamic tissue that responds to changes in loading such that the ratio of bone formation to removal in any one area will vary depending on the applied stress on the bone but is always in an ordered fashion so that one does not permanently predominate over the other

Front 13

The control of this bone balance is mediated largely through what? Via what


What is the modulation in RANKL production influenced by (2)

Back 13

The control of this balance is mediated largely through the osteoblast via the its production of growth factors such as RANKL.

The modulation in RANKL production is inturn 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 which respond to
loading by the production of cytokines such as
interleukin-1 (IL-1). The production of RANKL by
osteoblasts is increased by the action of IL-1.

Front 14

Maintenance of alveolar bone dependent upon? Explain

How else can this balance between formation and degradation be disrupted

Back 14

The maintenance of the alveolar bone is very much
dependant on sufficient load derived from the
presence of functioning teeth. If teeth are lost or
extracted (as in this case) then the alveolar bone will
be resorbed as the balance is upset and bone
degradation outstrips formation.

However, this balance between formation and destruction can also be tipped in the direction of bone resorption by the intervention of certain exogenous plaque bacterial derivedmaterial e.g lipo-polysaccharide (LPS) and bacterial enzymes which directly or indirectly affect the cells and matrix in the gingival cuff region. The next slide shows the dramatic effects of periodontal
disease on alveolar bone.

Front 15

What do sheep suffer from

Back 15

Sheep suffer from a rapidly progressing form of periodontal disease, known colloquially as ‘broken mouth’.

Front 16

If we go back to our original ‘status quo’ situation but
now add in a bacterial plaque adjacent to the
epithelium what will happen

Back 16

If we go back to our original ‘status quo’ situation but
now add in a bacterial plaque adjacent to the
epithelium, 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.

Front 17

There is some evidence that lps can do what

Back 17

There is some evidence that LPS can act
directly on osteoblasts to upregulate RANKL
production and on monocytes to accelerate their
fusion to osteoclasts but the main effect is on
macrophages. In these cells it stimulates an increase
in, amongst other things, IL-1 production

Front 18

What are the targets for increased il1

Back 18

One of the targets for the increased IL-1 are osteoblasts where RANKL production is upregulated which in turn leads to further recruitment of monocytes and the formation of more osteoclasts. Another target for IL-1 are the numerous fibroblasts throughout the tissue.

Front 19

These cells are triggered to produce what...

What acts upon what

Back 19

Thesecells are 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 – something they would not normally
do.

Front 20

This in part leads to...

First it does what

Back 20

This in part leads to a net loss of matrix and is
aided further by the presence of bacterial-derived
collagenases. The IL-1 has two further effects.

First it also stimulates the fibroblasts to produce another
cytokine, interleukin 6 (IL-6). This cytokine increases
the effectiveness of RANKL in stimulating osteoclast
formation

Front 21

Secondly what can IL-1 do

Back 21

Secondly, IL-1 can directly act on the
osteoclast to upregulate cathepsin K production and
thereby increase the effectiveness of individual cells
in degrading the bone matrix

Front 22

What will happen finally

Back 22

Finally, of course, the extensive matrix degradation will in turn lead to major changes in loading on the bone and macrophages thereby adding another impetus to the bone loss process.

Front 23

What does the diagram provide

Back 23

provides a simplified picture of tissue
interactions in this region as many other cytokines
and growth factors may be involved. Nevertheless it
does give an indication of the complex interplay
between the cells and how there is an inevitable rise
in the rate of bone degradation, triggered by the
presence of plaque bacteria.

Front 24

Summarise the actions of lps

Back 24

LPS:
Acts on osteoblasts to upregulate RANKL production
Acts on monocytes to increase osteoclast formation
Acts on macrophages to upregulate IL-1 production

Front 25

Summarise the actions of IL-1

Back 25

IL-1:
Acts on osteoblasts to upregulate RANKL production

Acts on fibroblasts to upregulate IL-1 production

Acts on fibroblasts to upregulate IL-6 production (which in turn potentiates
RANKL)

Acts on fibroblasts to induce collagenase production

Acts on osteoclasts to upregulate cathepsin K production

Front 26

The presence of bacteria (and their constituents and by-products) within
the gingival sulcus can trigger an inevitable, and ultimately
catastrophic, alveolar bone loss in 3 interlinked ways:

Back 26

1. A direct stimulation of osteoclast formation

2. The production of an inflammatory response, including the
production of numerous cytokines (notably IL-1), which directly or
indirectly increases osteoclast formation and activity. There is also
extensive connective tissue breakdown which in turn leads to:

3. A loss of loading on the bone which can of itself result in further
bone loss.