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MSK Pathology & Clinical > Osteoarthritis > Flashcards

Osteoarthritis Flashcards

1
Q

What is OA? and What does it affect?

A

A degenerative disorder affecting the articular cartilage

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2
Q

Molecules involved in OA?

A

1) TGF-β (in OA TGF-β will be down-regulated)
2) Wnt-3a
3) Indian hedgehog pathways
4) Signaling molecules:
- Smad3
- β-catenin (in OA β-catenin will be down-regulated)
- HIF-2α

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3
Q

Population affected by OA?

A

more common in Women and Elderly

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4
Q

Can OA be caused by Sports-related traumatic injuries at all ages?

A

Yes, sports can lead to post-traumatic OA

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5
Q

OA is characterized by what?

A

1) Progressive erosion (degeneration, loss) of articular cartilage and
2) Associated reactive changes at the margin of the joints and in the subchondral bone

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6
Q

Epidemiology of OA?

A
  • Age dependent
  • After 65 years
  • More common in women
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7
Q

Joints involved in OA?

A

Weight bearing joints > Hips, knees, cervical and lumbosacral spine

Other joints > DIP & PIP

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8
Q

What are the types of OA?

A

Primary > aging phenomenon > older individuals

Secondary > a predisposing condition > younger individuals

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9
Q

List Risk factors of OA (Dr,Ouban slide)

A

Trauma
Obesity
Ochronosis
Hemochromatosis

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10
Q

List Risk factors of OA (Modifiable & Non-modifiable)

A 
Modifiable
- Obesity
- Trauma
- Repetitive use (e.g., heavy labor)
Non-modifiable
- Age
- Female gender
- Family history
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11
Q

State the pathology mechanism of Age as a risk factor in OA

A

Aging chondrocytes > elevated oxidative stress > promotes
1) cell senescence
2) alters mitochondrial function
Disease progression > associated with mitochondrial dysfunction and cell death.

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12
Q

Why there is a reduced repair response in aging chondrocytes?

A

Due to alteration of the receptor expression pattern.

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13
Q

Discuss the pathological mechanism in OA related to age

A

1) In chondrocytes from aged and osteoarthritic cartilage, the ratio of TGF-β receptor ALK1 to ALK5 was increased
2) Leading to down-regulation of the TGF-β pathway and
3) Shift from matrix synthesis activity to catabolic matrix metalloproteinase (MMP/collagenases) expression.

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14
Q

Discuss the pathological mechanism in OA related to obesity

A

Low-grade systemic inflammation through secretion of

  • Adipokines
  • Pro-inflammatory cytokines > IL-1β, IL-6, IL-8 and TNF-α

These inflammatory factors may trigger NF-κB signaling pathway > stimulate an articular chondrocyte catabolic process > ECM degradation through the upregulation of MMPs

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15
Q

What causes epigenetic alteration in OA chondrocytes?

A

Changes in expression of Dnmts (methylation) and Tets (de-methylation) enzymes.

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16
Q

Does inflammation found in OA contributes to disease development and progression?

A

Yes

17
Q

What structures are involved in inflammation of OA?

A

Entire synovial joint, including:

  • Cartilage,
  • Subchondral bone
  • Synovium
18
Q

What is the mechanism of inflammation in aging and diabetic patients?

A

IL-1β, TNF-α & chemokines > contribute to the systemic inflammation > activation of NF-κB signaling in both synovial cells and chondrocytes.

19
Q

What innate inflammatory signals are involved in OA?

A
  • DAMPs
  • Dlarmins (S100A8 and S100A9)
  • Complement
20
Q

What are the role of innate inflammatory signals in OA?

A

DAMPs and alarmins were abundant in OA joints, signaling through either
- TLR or
- The canonical NF-κB pathway
> to modulate the expression of MMPs and ADAMTS in chondrocytes

21
Q

How complement can be activated in OA chondrocytes and synovial cells?

A

By,

  • DAMPs,
  • ECM fragments
  • Dead-cell debris.
22
Q

What does systemic inflammation do in OA?

A

Re-program chondrocytes through inflammatory mediators toward hypertrophic differentiation and catabolic responses

23
Q

What inflammatory mediators involved in systemic inflammation in OA?

A
  • NF-κB pathway
  • ZIP8/Zn+/MTF1 axis
  • Autophagy mechanisms
24
Q

How Genetic predisposition contributes in OA?

A
  • Alterations in TGF-β, Wnt/β-catenin
  • Ihh, Notch and FGF pathways > contribute to OA development and progression by primarily inducing catabolic responses in chondrocytes

Such responses converge on

1) HIF-2α
2) Runx2
3) Inflammatory mediators > cartilage ECM degradation through increased expression of MMPs and ADAMTS activity

25
Q

What is the role of RUNX2? and what happens if it’s down-regulated?

A

Key transcription factor associated with osteoblast differentiation & to maintain ECM.

RUNX2 down-regulation > no maintenance of ECM

26
Q

Recent studies of genome-wide association screens (GWAS) revealed what?

A

Over 80 gene mutations or single-nucleotide polymorphisms (SNPs) involved in OA pathogenesis.

Some genes are

1) important structural and ECM-related factors (Col2a1, Col9a1, and Col11a1), and
2) critical signaling molecules in the Wnt (Sfrp-3), BMP (GDF5), & TGF-β (Smad3) signaling pathways

27
Q

Discuss knee joint changes/findings in OA

A

1) Thinning of articular cartilage
2) Development of cracks & fibrillation
3) Erosion and loss of cartilage
4) Formation of : Loose bodies (Joint mice) & Subchondral cyst
5) Eburnation (conversion of the sub-chondral bone to an ivory-like surface at the site of the cartilage erosion)
6) Sclerosis
7) Osteophyte (bony outgrowths at joint margins) develop due to bone remodeling, seen in
- DIP joint as Heberden nodes
- PIP joint as Bouchard nodes
8) Narrowing of joint space
9) Degeneration of ligaments and menisci of the knee
10) Hypertrophy of the joint capsule

28
Q

State function of cartilage

A

Cartilage lubricated by synovial fluid, cushions the bones and allows friction less motion

29
Q

State gross & microscopic appearance of advanced cases in OA

A

Gross: Eburnated bone which is shiny and smooth
Microscopic: sclerotic

30
Q

List OA Clinical findings

A

1) Pain with passive motion of joint, due to secondary synovitis
2) Joint stiffness
3) Crepitus
4) Heberden’s nodes
5) Bouchard’s nodes

31
Q

What are the radio-graphic findings of OA?

A

1) Presence of osteophytes at joint margins
2) Subchondral bone cysts
3) Joint space narrowing
4) No ankylosis* (fusion) of joint

32
Q

Loss of articular cartilage is due to?

A
  • Genetic
  • Chemical
  • Inflammatory
33
Q

Describe stiffness in OA

A

It worsens throughout the day because OA itself is an activity & movement related

MSK Pathology & Clinical (15 decks)

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