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Perio I > 8. Pathogenesis of Periodontal Disease > Flashcards

8. Pathogenesis of Periodontal Disease Flashcards

1
Q

Periodontopathogens Virulence factors

____ gram - ____ bacteria

Adhesion (____)
____
Endotoxin (____) Bacterial enzymes …

LEADS TO

____ or ____ tissue destruction

A 
anaerobic
negative
fimbriae
invasins
LPS

direct
indirect

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2
Q

Influential Factors

____, local and ____ factors: Diabetes, ____, immune diseases…patient

• Obesity and diabetes increase the \_\_\_\_ cytokines
A

systemic
environmental
pro-inflam

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3
Q

Matrix Metalloproteinases

ü Degradation of ____
ü ____ and ____ conditions
ü ____ in periodontal disease

* MMP released in \_\_\_\_ form, that must be then activated
* \_\_\_\_ levels of MMP are always present - helps in remodeling
* Can check as a biomarker in \_\_\_\_
A 
ECM
normal
pathological
biomarker
inactive
low
GCF
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4
Q

Roles of MMPs (Enzymes)
• ____
• Regulation: ____, ____
• Removal of ____ matrix

A

degradation
cytokines
osteoclastogenesis
organic

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5
Q

Effect of cranberry compounds on matrix metalloproteinases

Cranberry
• Vaccinium ____
• Rich in ____
• Well-Known for beneficial effects in ____ infection
• ____ (non dialysable material, 65% proanthcyanidins) obtained by dialyzed concentrated cranberry juice showed beneficial effects in oral health (Dental carries and periodontal disease)
• ____ (A-type cranberry proanthocyanidins) are well characterized and being used in different studies.

* Powerful \_\_\_\_
* UTI - juice prevents the bacteria from attaching during infection
A 
macrocarpon
polyphenols
urinary tract
NDM
AC-PACs

antioxidant

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6
Q

Effect of AC-PACs on the production of MMPs by human macrophages

Differentiation of U937 into ____ > +- PACs, Aa ____, ____degC, 24 hr > Supernatant collection > ____ (MMPs, -1, -3, -7, -8, -9, -13)

A

macrophages
LPS
37
ELISA

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7
Q

Effect of AC-PACs on the production of MMPs by human macrophages

First column is just the cell itself
Second is aBer trea5ng with LPS, it ____

Treatment with different concentra5ons of PAC decrease in ____ dependent manner. If somehow we
have a carrier to bring extract into body somewhere where MMP is secreted, you can clam down
bacteria with ____ . That’s the whole purpose.

A

increases

dose
virulence

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8
Q

Effect of AC-PACs on the activity of human recombinant MMP-1 & -9

MMP is released in our body in ____ form. In order to express ac5vity they must be ac5vated. You
can buy MMP from the lab company that makes human recombinant MMP. We ac5vated them.
When you ac5vate them you treat them with different concentra5ons, and again it very nicely
decreases ____. It is seen to be dose dependent.

This shows a well known control for MMP inhibitor. So this one is very well known one used as
posi5ve sample. Really bring it down here but MMP is even stronger. When the concentra5on is not
comparable. This PAC can reduce the produc5on and ac5va5on of MMP. But how do they do that?
We actually go one step further…

A

inactive

MMP

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9
Q

Effect of AC-PACs on NF-kB p65 activation induced by A.actinomycetemcomitans LPS

+- PACs, Aa LPS: 1h > Cell extract > ____ p65

We will look into the mechanism or the pathway. NFKB is the main pathway for ____
cytokine produc5on.
We s5mulate macrophages with AA LPS for a very short one hour to a5vate cellular nucleaus. We
then break down the cell and measure the ac5va5on of NF-kB.
1. No ____ the cell is very calm.
2. S5mulate with LPS. Highly ac5vated
3. Then bring it back down with ____.

A

NFkb
pro-inflam
LPS
PACs

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10
Q

Roles of Inflammatory Cytokines
• ____ - Edged Sword !!!
• Upregulation of the ____ and ____ immune responses
• Upregulation of the ____ formation

A

double
innate
acquired
osteoclast

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11
Q

Receptor Activator of Nuclear Factor Kappa-β Ligand (RANKL)

  • Produced during ____ and ____ conditions
  • One of the primary factors towards ____(Formation and Functions)
  • Inhibited by ____
A

physiologic
pathologic
osteoclasts
osteoprotegrin (OPG)

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12
Q

Cytokines & Periodontal Disease

• \_\_\_\_, \_\_\_\_, and \_\_\_\_ induce RANKL secretion
A

TNFalpha, IL1, IL6

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13
Q

Periodontal Disease Osteoimmunology

* In health, \_\_\_\_ cells release RANKL, and once the precursor binds RANKL > formation of \_\_\_\_
* OPG binds RANKL and inhibits \_\_\_\_ formation
* Bacteria results in the production of a large amount of \_\_\_\_
A

bone lining
OC
OC
RANKL

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14
Q

Naringenin

  • Naturally occurring ____ found in ____ fruits: grapefruit, tomato…
  • ____, anticancer, antiinflammation, anti-____…
  • ____ disease?
A 
flavonoid
citrus
antioxidant
HCV
periodontal
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15
Q

Human Macrophage Model

Differentiation of U937 into ____ > +- Naringenin, Aa ____, ____degC, 24 hr > Supernatant collection > ____ IL-1b, IL-6, IL-8, TNF-a

A

macrophages
LPS
37
ELISA

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16
Q

Human Macrophage Model

So again, very similar produc5on of similar cytokines is reduced by non toxic concentra5ons of ____. This is good because reducing ____ and ____.

But actually, at very low concentra5on, naringenis is more ____ to proinflamatory cytokines but when you go a liLle higher in concentra5on it is reduced (____ concentra5ons).

A

narinogenin
IL-1b
IL-6

stimulating
non-toxic

17
Q

Ex-vivo Human Whole Blood Model

Whole ____ collection > Dilution ____ Aa LPS, 37degC, 6 h > supernatant collection > ____ IL-1B, IL-6, IL-8, TNF-alpha

A

blood
1/3
ELISA

18
Q

Ex-vivo Human Whole Blood Model

Strong inhibition of ____ and ____ secretion

A

TNF-alpha

IL-1b

19
Q

Naringenin has anti-inflammatory properties in ____ and ex vivo human ____ models

A

macrophages

whole-blood

20
Q

Osteoclastogenesis
Human Osteoclast Precursors activated by ____ and ____

* When culture monocyte with RANKL, they fuse and form \_\_\_\_
* \_\_\_\_ stain > multinuclear > OC
A

MCSF
RANKL
OC
TRAP

21
Q

Osteoclastogenesis

• Reduce the production of inflam cytokines (\_\_\_\_ and \_\_\_\_), and reduce the formation of \_\_\_\_
A

TNFalpha
IL1b
OC

22
Q

Osteoclastic bone resorption

Human osteoclast ____: MCSF + RANKL
AND
____ human ____ plates

>

____ released

>

+- naringenin in new medium for 48h

>

monitor collagen helical peptide a1 by ____

• Upon resorption of \_\_\_\_ > release CHPa1
A

precursors
osteoassay
human

collagen helical peptide a1

ELISA

bone

23
Q

Osteoclastic bone resorption

• \_\_\_\_ concentration of CHPa1 is released with \_\_\_\_ naringeninc
A

small

increased

24
Q

Naringenin inhibits human ____ and osteoclastic bone ____

A

osteoclastogenesis

resorption

25
Q

Take home messages

Host response could be both ____ and ____

A

protective

destructive

Perio I (10 decks)

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