Gingival Overgrowth

Question 1

causes of gingival overgrowth

Answer 1

medication side effects
inherited - fibromatosis
idiopathic (no one knows why)

Question 2

Phenytoin

Answer 2

drug that causes side effect of gingival overgrowth characterized by increase in FIBROTIC/HARD TISSUE GROWTH

Question 3

Nifedipine

Answer 3

drug that can cause gingival overgrowth characterized by a mixture of increased fibrottic tissue and inflammation

Question 4

Cyclosporin A

Answer 4

drug that can have a side effect of causing gingival overgrowth and most commonly causes inflammation

given to treat immunosuppresent individuals so inhibits the acquired immune response –> so the innate becomes exxagerated

Question 5

Phenytoin, Nifedipine, and Cyclosporin A are all?

Answer 5

drugs that can cause the side effects of gingival overgrowth

Question 6

Features of gingival overgrowth

Answer 6

1. varying degrees of inflammation and fibrosis
2. THICKENED EPITHELIUM -> no matter the kind of gingival overgrowth this will be seen
3. thickened connective tissue

can all have negative effects on oral hygeine, more bacteria has spaces and spots to attack and can cause systemic problems potentially?

Question 7

two types of gingival overgrowth and their characteristics

Answer 7

fibrotic overgrowth and inflammatory overgrowth

Question 8

what will thickened epithelium show histologically?

Answer 8

RETE PEGS INCREASE IN ALL TYPES - spikes or pegs from epithelium going into the connective tissue

also…there will ALWAYS be some level of inflammation (just depends on amount that is determining factor)

Question 9

what area of gingiva may have the most inflammation?

Answer 9

sulcular epithelium

Question 10

CTGF (CNN2)

Answer 10

molecular marker (grwoth factor) that is upregulated in FIBROTIC gingival overgrowth - so elevated in phenytoin and Nifedipine induced gingival overgrwoth

upregulated by TGF-beta
matricellular protein
strongly promotes fibrosis

BUT IS DOWN REGULATED IN NON ORAL CELLS LIKE LUNG AND KIDNEY

Question 11

CCN2 in non oral cells

Answer 11

DOWNREGULATED and basically shut off by inflammatory mediators like TNF-alpha and PGE2
like in lung and kidney cells

WHEN THERE IS INFLAMMATION PRESENT IN NON ORAL TISSUES CCN2 IS SHUT OFF BY THESE

Question 12

TNF-alpha and PGE2

Answer 12

down regulate inflammation like CCN2 in tissues in cells NOT IN THE ORAL CAVITY –> PGE2 does not block the expression of CNN2 in the oral cavity

but when have gingival inflammtion and majorly fibrotic overgrowth due to PHE - the CNN2 resists the down regulation of the PGE and TNF-alpha - supporting that there is different fibroblasts in the oral cavity than in other places like the lung and kidney

Question 13

receptor for PGE2

Answer 13

EP3 –> stimulate the JNK pathway to increase the CTFG expression –> more tgf-beta and cnn2

EP2/4 –> inhibitory of the JNK and thus reduced CTFG expression through adenylate cyclase –> cAMP–> PKA–> inhibit the JNK

Question 14

ERK, p38

Answer 14

receptors for TGF-beta? – increase the CTGF expression

Question 15

Lovastatin

Answer 15

inhibitor of HMG-CoA reductase which will inhibit the biosynthetic pathway of cholestroel and thus reduce production of FA that are incorporated onto Ras and Rho that can contribute to the expression of CTGF through the activation of Rac1/cdc42

Question 16

FTI

Answer 16

Farnesyl Transferase inhibitor - inhibits the phosphorylation that occurs to incoporate the FA onto the Ras –> so decreases or inhbits RAS ability to acitvate the CTGF expression through the Rac1/cdc42

Question 17

GGTI

Answer 17

same thing as for the FTI but inhibiting the Geranyl-geranyl transferase that increases the RHO gtpases

Question 18

Forskolin

Answer 18

can increase cAMP which ultimately inhibits CCN2/CTGF production in the presence of TGF-beta in gingival fibroblasts

Question 19

statins

Answer 19

inhibit the HMGCo reductase that ultimately inhibits CCN2/CTGF production in the presence of TGF-B in gingival fibroblasts

Question 20

Epithelial transition in gingival overgrowth

Answer 20

epithelial to MESENCHYME gingival overgrowth

this increases the motility of cells, proliferation, and invasion into the connective tissue (why we see the rete pegs more)

Question 21

E-cadherin

Answer 21

epithelial cell surface protein that is critical for cell-cell contact and interaction

see loss of expression in this at basement membrane - showing consistency in notion of the epithelial to mesenchymal transition and increase in the rete pegs