Cartilage

Question 1

Only cell type found in cartilage

Answer 1

Chondrocytes

Question 2

Collagen type II and proteoglycans make up the __________ of cartilage

Answer 2

Matrix

Question 3

~75% total weight of cartilage

Answer 3

Water

Question 4

Does cartilage tissue contain blood vessels?

Answer 4

No

Question 5

Does cartilage tissue contain blood or immune cells?

Answer 5

No

Question 6

How do chondrocytes attain nutrients?

Answer 6

Diffusion from blood vessels outside the perichondrium

Question 7

A dense CT layer surrounding hyaline cartilage

Answer 7

Perichondrium

Question 8

Two layers of the perichondrium

Answer 8

1. outer, dense CT, collagen I

b. inner chondrogenic layer, fibroblasts differentiate to chondrocytes

Question 9

Mechanism for cartilage growth were new matrix is laid down on the cartilage surface by cells in the inner layer of the perichondrium.

Answer 9

Appositional growth

Question 10

Mechanism for cartilage growth where chondrocytes in the interior divide and secrete matrix between them. Cartilage swells from within, like bread rising.

Answer 10

Interstitial growth

Question 11

Actively secreting new matrix even in mature cartilage
Abundant RER - mostly secretes proteoglycans (and some cartilage type II)
Found in lacuna

Answer 11

Chondrocyte

Question 12

What features can help tell you that you are looking outside of the cartilage and perichondrium?

Answer 12

Glands and blood vessels

Question 13

Why are proteoglycans in the collagen matrix darkly staining?

Answer 13

They have a negative charge

Question 14

Due to the increased concentration of proteoglycans, the territorial matrix of hyaline cartilage stains ______

Answer 14

Darkly

Question 15

________ cartilage provides mechanical support, to keep the airway open

Answer 15

Tracheal

Question 16

What is the function of cartilage in the ear?

Answer 16

Keeps the ear semi-rigid

Question 17

___________ cartilage is the most important and is found in joints

Answer 17

Articular

Question 18

Articular cartilage is important for two major things:

Answer 18

1. Friction free movement at joint

2. Mechanical cushion at joint

Question 19

Covers the bone surfaces where they “articulate” at a joint

Forms a slippery, friction-free surface
No perichondrium, cartilage matrix slides against cartilage matrix

Provides a shock absorbing cushion. The cartilage supports the full weight, same as the bone, but it is compressible (a lot of water - when compressed the matrix squeezes out water, when relaxed the water is sucked in)

Answer 19

Articular cartilage

Question 20

Articular cartilage acts as a mechanical cushion - like an inner-spring mattress where:
____________ are the springs, and ____________ (2 things) make the framework

Answer 20

Proteoglycans are the springs

Collagen Type II and hyaluronic acid make the framework

Question 21

A protein with one or more carbohydrate clusters covalently attached to asparagine and/or ser/thr residues.
Accounts for most extracellular proteins
Can be 1-60% carbohydrate by weight

Answer 21

Glycoprotein

Question 22

A dozen or more sugar molecules attached to each other in a branched cluster

Answer 22

Carbohydrate cluster

Question 23

Long (50-100 sugars), unbranched chain of repeating disaccharides
Many of the sugars have COO- and OSO2- groups, making an overall negative charge throughout
Almost all are attached to a protein

Answer 23

Glycosaminoglycan (GAG)

Question 24

Hyaluronic acid and heparin are unusual in that they exist as free _________ not covalently attached to a core protein.

Answer 24

GAGs

Question 25

Most ________ are attached to a core protein to make a proteoglycan

Answer 25

GAGs

Question 26

Chondroitin sulfate and keratan sulfate are examples of _________

Answer 26

GAGs

Question 27

A protein with carbohydrate clusters

Answer 27

Glycoprotein

Question 28

A protein with GAGs attached and consists of a core protein (extended polypeptide) with several or many GAGs attached Ex. Syndical, a cell surface receptor with 3-6 GAGs only (90% protein) Negatively charged chains Assistants for binding growth factors

Answer 28

Proteoglycan

Question 29

Large aggregating proteoglycan of cartilage

Answer 29

Aggrecan

Question 30

_____________ charged GAGs repel each other, both intra and inter molecularly. Pressure can compress the GAGs, squeezing out water.

Answer 30

Negatively

Question 31

_____________ molecules are already highly compressed in articular cartilage, to 1/3 their relaxed volume. Additional pressure on the joint causes a further compression, squeezes water into the joint capsule. When the pressure is releases, the proteoglycans expand and take back the water.

Answer 31

Aggrecan

Question 32

What is the basic structure of aggrecan?

Answer 32

Core protein, with protruding chondroitin sulfate chains and keratan sulfate chains, O-,N-lnked oligosaccharides, and a hyaluronic acid binding domain 300 nm long, but 700 nm if fully extended

Question 33

Cartilage matrix is pre-stressed. Aggrecan molecules are compressed and packed ____ their relaxed density in solution. This makes the articular cartilage very hard.

Answer 33

3X

Question 34

The two components of the framework that keeps aggrecans from flying apart:

Answer 34

1. Attachement to hyaluronan | 2. Collagen II network, entrapment

Question 35

How is hyaluronic acid (hyaluronan) a unique GAG?

Answer 35

1. Not attached to a core protein (almost all are expect heparin and hyaluronic acid) 2. COO- but no SO4- (less charged) c. Huge (25,000 sugars, 10,000,000 Da, 40 microns long)

Question 36

______________ is a major component of "ground substance" of loose CT. Makes a viscous hydrated gel and plays a key role in cartilage architecture. Traps proteoglycans through their binding domain. Long chain of repeating disaccharides that is 100x longer than collagen.

Answer 36

Hyaluronic acid

Question 37

A random 3D network of __________ fibrils entraps proteoglycan aggregates and prevents the loss of aggrecan.

Answer 37

collagen type II

Question 38

HA binding domain attaches aggrecans to a long hyaluronic acid molecule. This makes the:

Answer 38

proteoglycan aggregate

Question 39

___________ fibrils makes a 3D network. The proteoglycan aggregate is entrapped by snaking through the collagen network.

Answer 39

Collagen II

Question 40

Some loss of proteoglycans does occur. ______________ need to continuously synthesize new ones.

Answer 40

Chondrocytes

Question 41

Glassy Found in trachea, bone primordia and growth plate Articular cartilage Most common type of cartilage

Answer 41

Hyalin cartilage

Question 42

Like hyaline, but includes elastic fibers | Found in the ear

Answer 42

Elastic cartilage

Question 43

A mixture of dense CT (collagen I) and small islands of chondrocytes surrounded by cartilage matrix In tendons and ligaments, especially where subject to compression, and intervertebral disks

Answer 43

Fibrocartilage

Question 44

______________ makes tendons compressible

Answer 44

Fibrocartilage

Question 45

_______________ of the joint capsule secretes fluid into the joint cavity

Answer 45

Synovial membrane

Question 46

Torn tendons are readily repaired. If ends are reasonably juxtaposed, ____________ make new collagen fibrils, join them to the existing fibers. Remodeling molds tendon to match the forces it sees.

Answer 46

fibroblasts

Question 47

_______________ repairs only poorly. A fracture here may be filled in with fibrocartilage, but the friction-free movement is compromised.

Answer 47

Articular cartilage

Question 48

Broken bones repair if the ends are:

Answer 48

set in contact

Question 49

____-negataive neuroectoderm cells have enhanced regenerative capacity.

Answer 49

Hox

Question 50

Neural crest-derived cells may be able to be used for _____________ repair.

Answer 50

articular cartilage

Question 51

Inflammatory disease, focused on the joints Activated macrophages and lymphocytes secrete proteases that attack the cartilage matrix Systemic autoimmune disorder, principally affecting synovial joints

Answer 51

Rheumatoid arthritis

Question 52

Cytokine, originally discovered as a factor secreted by lymphocytes that kill tumor cells When released in quantity, it causes cachexia When released focally in RA joint, it induces other inflammatory cytokines - leads to erosion of articular cartilage and the underlying bone

Answer 52

TNF alpha | Tumor necrosis factor alpha, cachexin, cachectin

Question 53

TNF alpha released by ______________ is a key link to RA. TNFa is released with histamine and heparin and other cytokines.

Answer 53

mast cells

Question 54

Treatments for RA

Answer 54

Small molecule inhibitors of immune and inflammation: methotrexate (MTX) Anti-inflammatory agents and analgesics: glucocorticoids, NSAIDS Biologics

Question 55

Generally a protein with therapeutic properties Made is bacteria or mammalian cell culture, purified and tested (mAb or recombinant proteins)

Answer 55

Biologic (biopharmaceutical) Biosimilar = generic

Question 56

Two biologic treatments for RA

Answer 56

1. mAB against TNF alpha: humira (adalimumab) - #1 selling drug in the world 2. Recombinant protein, produced in bacteria or cultured cells: enbrel (entanercept), a decoy TNFalpha receptor that binds and sequesters TNFa

Question 57

A complex set of diseases, involving: a. wear and tear degradation of articular cartilage b. genetic factors c. accompanied by inflammation, milder than in RA but similar in many respects (modern treatment bridges the two) More common than RA

Answer 57

Osteoarthritis

Question 58

Treatments for osteoarthritis

Answer 58

Pain killers, corticosteroids, and/or anti-inflammatories injected into the joints Eventually joint replacement Treatments more limited than for RA