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MSK > Cartilage regeneration and repair > Flashcards

Cartilage regeneration and repair Flashcards

1
Q

How is the turnover of cartilage?

A

Cartilage has limited intrinsic regeneration capacity

Low turnover of tissue

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2
Q

Fetal cartilage can regenerate completely

TRUE or FALSE

A

TRUE

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3
Q

Remodeling capacity of cartilage tissue

A

Cartilage is prone to several insults related to increased joint mechanical loading

Chondroctes can in a limimted manner repair cartilage defects

Matrix however shows poor lateral integration

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4
Q

What are features of osteoarthritis?

A

Chronic degeneration of cartilage tissue matrix

Leads to a loss of joint function

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5
Q

What happens to the severity of OA if subchondral bone is involved?

A

Condition is exacerbated

Cells invading from subchondral bone synthesize collagen type I ECM

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6
Q

What causes the changes in cartilage in OA?

A

Chondrocytes alter their gene expresssion profile

Make a catabolic phenotype

Synthesize increased levels of proteolytic enzymes that degrade cartilage ECM

Degradation of these componenets leads to weakening of the cartilage ECM

Causes roughening of the cartilage tissue and deep fibrillation of the matrix

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7
Q

What are examples of enzymes released by chondrocytes that damage cartilage?

A

Collagenases - degrade collagen (MMP-13)

Aggrecanases - degrade aggrecan (ADAMTS5)

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8
Q

What happens to the chondrocytes in OA?

A

Proliferate by a process of clonar expansion and die

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9
Q

What increases the chances of developing OA?

A

Obesity

Age

Gender

Inflammation

Genes and epigenetics

Over-use of joints

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10
Q

What happens to the bones of OA patients?

A

Thickening of the subchondral bone following reactive remodelling

Leads to the formation of osteophytes, bone cysts and epiphyseal expansion

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11
Q

Why do bones change during OA?

A

Represent mechano-adaptation of the bone to the altered mechanical environment

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12
Q

Can changes to the bone during OA be observed?

A

Yes

These changes are diagnostic on plain radiographs

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13
Q

What are osteophytes?

A

Form by a process of endochondral ossification

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14
Q

What is a key early event in the pathogenesis of OA?

A

Degradation of aggrecan by aggrecanase

Aggrecan protects collagen from proteolytic degradation

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15
Q

Is aggrecan degradation reversible?

A

Yes

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16
Q

Is collagen degradation reversible?

A

No

17
Q

What are MMPs?

A

Matrix metalloproteinases

Calcium-dependent

Degrade collagen molecules and other ECM proteins

Calcium-dependent zinc-containing endopeptidases

Synthesized as inactive zymogens with pro-peptide domain

18
Q

What does ADAMTS stand for?

A

A disintegrin and metalloproteinase with thrombospondin motifs

19
Q

Deletion of catalytic domain of ADAMTS5 in transgenic animal confers resistance to cartilage destruction

TRUE or FALSE

A

TRUE

20
Q

What type of condition is Achondroplasia?

A

Autosomal dominant mutation

Characterised by shortened limbs

21
Q

What causes Achondroplasia?

A

Caused by constantly active FGF receptor 3

Causes inhibition of chondrocyte proliferation and differentiation

Reduced size of cartilage anlagen

Impairs endochondral ossification

Reduced bone growth as growth plate function is impaired

22
Q

Does Achondroplasia affect all the bones?

A

NO

Only the ones formed through endochondral ossification

Not the ones formed through intramembranous ossification

23
Q

What is rheumatoid arthritis?

A

Severely debilitating, painful degenerative joint disease

Autoimmune disease

Progressive destruction of the joints by immune cells

24
Q

What is the presentation of RA?

A

Chronic inflammation of the joints

Deformation and loss of motility/ joint function

25
Q

What are the treatments for RA?

A

No curative treatments available

Therapy using anti-inflammatory drugs

Novel biologics to block immune response

26
Q

What is essential to improve outcome of RA?

A

Early diagnosis

Tailored therapy

27
Q

Describe a clinical trial targeted at RA

A

Intraarticular interleukin-1 receptor antagonist gene therapy

28
Q

Describe the process of Matrix-assisted chondrocyte implantation

A

Adult chondrocyte isolated from non-load bearing part of hyaline cartilage

Patient-specific chondrocytes are expanded in in vitro culture

Cells are re-implanted into defect

Covered in synthetic membrane (allogenic collagen membrane or periost)

29
Q

How do you obtain the chondrocytes from the non-load bearing parts of the hyaline cartilage?

A

Extract material

Tissue is digested

30
Q

What are the problems with MACI?

A

Conservation of chondrogenic phenotype during 2D expansion

Cost

Donor site morbidity

31
Q

What were the results of MACI?

A

Good results in younger patients

Not always reproducible

MSK (22 decks)

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