Monday: Physiology and Biochem of Cartilage and Synovial Fluid Flashcards

1
Q

Adult cartilage has ____ cell density compared to its extracellular matrix.

A

Low cell density

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2
Q

What are three regions of extracellular matrix?

A
  1. Pericellular matrix (thin rim around cell)
  2. Territorial matrix (around pericellular matrix enclosed by thin fibrils)
  3. Interterritorial matrix (bulk of cartilage matrix).
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3
Q

What is term to refer to chondrocyte in pericellular matrix?

A

Chondron

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4
Q

Articular cartilage can withstand compressive loads what times body weight?

A

3-5x body weight while providing smooth surface of repeated joint movement without significant cell division.

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5
Q

What is percentage division of cartilage make-up?

A

65-80% Water
10-20% collagens
5-10% proteoglycans

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6
Q

Why is cartilage firm and resilient?

A

Interaction of collagen fibrils with highly charged proteoglycans

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7
Q

What is organization of articular cartilage? Four zones

A
Subchondral bone 
--------------
1. Calcified zone
Tide mark
2. Deep zone
3. Middle zone
4. Superficial zone
------- Articular surface
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8
Q

Pericellular region contains what?

A

High concentration of aggrecan, proteoglycan decorin, and Type VI collagen.

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9
Q

Superficial zone contains…

A

thin collagen fibrils arranged parallel to articular surfaces

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10
Q

What is difference between Type II and Type I collagen?

A

Type II is composed of three identical chains that form triple helical structure typical of collagen.

Type I collagen has two identical chains and one chain with slightly different amino acid composition.

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11
Q

Type XI collagen is…

A

Fibrillar collagen that affects diameter of type II collagen fibrils.

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12
Q

Genetic defects in type II and XI collagens have been identified in families with…

A

Stickler syndrome (disorder involving premature development of osteoarthritis).

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13
Q

Type IX collagen is..

A

Glycosylated collagen on surface of fibril and is involved in noncovalent attachment of collagen fibril to other matrix macro-molecules.

Important in maintaining cartilage integrity.

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14
Q

Type X collagen is…

A

Short chain collagen and is synthesized primarily by hypertrophic chondrocytes found in growth plate and below tidemark in calcified zone of articular cartilage.

Type X is associated with cartilage undergoing calcification.

In osteoarthritis, type X collagen is found above tidemark.

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15
Q

What are proteoglycans?

A

Core protein with multiple glycosaminoglycans covalently attached to core.

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16
Q

Largest and most abundant proteoglycan in cartilage is…

A

Aggrecan

Has classic bottle brush structure due to multiple chondroitin sulfate and keratan sulfate glycosaminoglycans attached to core protein.

17
Q

Aggregan secreted from chondrocyte and associates with long nonsulfated glycosaminoglycan called…

A

Hyaluronan

aka Hyaluronate and formerly called Hyaluronic acid.

Up to 200 aggregan molecules can associate with a single hyaluronan molecule forming a large proteoglycan aggregate.
Aggrecan binds noncovalently through its N terminal or G1 domain.

18
Q

Attachment of aggrecan to hyaluronan is stabilized by small glycoprotein called…

A

Link protein

19
Q

What are GAGs?

A

Linear polysaccharides composed of repeating disaccharide units usually more than 20 per chain.

GAGs have negative charges along length of chain (COO-) and these are neutralized by number of cations which have water molecules associated with them.

20
Q

Collagen fibrils restrict volume of proteoglycan aggregates. How do this affect cartilage?

A

Pushes negatively charged groups together and results in strong repulsive force which produces swelling pressure of cartilage.

21
Q

What is fibronectin?

A

Matrix molecule that forms long fibrils and has multiple binding sites for other matrix molecules including collagen and heparin sulfate and for integrins on surface of chondrocytes.

Fibronectin is elevated in osteoarthritic cartilage.

22
Q

What is decorin?

A

Decorin decorates outside of collagen fibrils and is involved in regulation of fibril assembly.

Decorin and biglycan bind growth factor TGF-alpha and stores growth factor in matrix.

23
Q

What is link between matrix macromolecules and between chondron and other matrix components?

A

Type VI collagen.

Also elevated in osteoarthrtici cartilage.

24
Q

Laminin is a glycoprotein found in chondron and has what function?

A

Development and cell differentiation.

25
Q

What synthesizes and secretes new cartilage matrix macromolecules, enzymes that degrade matrix, and inhibitors of those enzymes.

A

Chondrocytes

26
Q

How do chondroctyes respond to IL1, TNFalpha, and cytokines?

A

Decreasing synthesis of proteoglycans and collagens. Increasing synthesis of matrix-degrading enzymes.

27
Q

IL1 is synthesized by many cells in the body including… TNFalpha is produced by…

A

IL1=chondroctyes

TNFalpha=mononuclear phagocytes

28
Q

Effects of IL2 on chondrocytes are mediated by…

A

NO

Elevated in RA and osteoarthritis.

29
Q

What are main mediators of matrix degradation?

A

Matrix metalloproteinases (MMP).

Osteoarthritis=Increased matrix catabolism and decreased levels of MMP inhibitors.

30
Q

What degrades proteoglycans?

A

Cathepsin B (can activate strome-lysin-1).

31
Q

Movement of cartilage against cartilage at low velocity needs ____ lubrication.

A

Boundary lubrication

Provided by lubricin (small glycoprotein), surface active phospholipids, and proteolipids.

32
Q

Movement of cartilage against cartilage at high velocity needs ________.

A

Elastohydrodynamic lubrication.

33
Q

How is synovial fluid different from plasma?

A

Lower protein content
Higher percentage of albumin
Lower alpha-2-globulin.

34
Q

What allows passage of proteins into synovial fluid?

A

Endothelial cells in capillaries.

35
Q

What regulates passage of small molecules into synovial fluid?

A

Synovial interstitium

O2, glucose, CO2, lactate, etc

36
Q

How does alk phos get into synovial fluid?

A

May arise from cartilage (by lining cells and secreted into synovium).

37
Q

Does clot form between fracture surfaces in a joint?

A

Clot does form but poorly organized and rapidly removed from joint fluid.

Articular cartilage and synovium release activator of plasminogen (proteolytic enzyme). This enzyme breaks down fibrinogen and prevents formation of firm clot.