Lecture 3 - Quiz 1

Question 1

What is the ECM?

Answer 1

Extracellular matrix - any substance produced by cells and secreted to the extracellular space within the tissues - connective tissue

Question 2

What are fibroblasts and their structure?

Answer 2

Fibroblasts have elongated nuclei and cytoplasms, and synthesize and maintain all the ECM components

Question 3

What are tenocytes?

Answer 3

The fibroblasts of the tendons that maintain the ECM - principally collagen

Question 4

What gives ECM tension and compression resistance?

Answer 4

Collagen crosslinks for resistance to tension and proteoglycans give resistance to compression

Question 5

What are the roles of ECM?

Answer 5

Hold tissues together for structural support, comportmentalize tissues from one another and regulate intercellular communication by cell signaling - promotes and inhibits growth factor signals - essential for growth and wound healing

Question 6

How does the ECM promote and inhibit GF signals?

Answer 6

Promotes by pericellular matrix (PCM) molecules binding and localizing GF close to cell surface to promote binding to receptor, in hibits when ECM/PCM molecules bind GF and sequester it away from the receptors

Question 7

What is the structure of the PCM for chondrocytes?

Answer 7

PCM made up of hyaluronic acid with red blood cells kept at a distance from the chondrocytes

Question 8

What are the components of the ECM?

Answer 8

Ground substance - like adhesive glycoproteins like laminin and fibronectin play a role in the adhesion of the cells and glycosaminoglycans (GAGs) give a hydrate gel for resistance to compressive forces and fibers - provide tensile strength and elasticity with collagens and elastins

Question 9

What are the classifications of GAGs?

Answer 9

Heparin, chondroitin, keratan - all sulfates to give negative charge to bind a lot of water
Hyaluronic acid HA - non sulfated
Make up proteoglycans

Question 10

What do GAGs do and what is their structure?

Answer 10

Provide a hydrate gel to resist compressive forces - polysaccharides composed of linear repeated disaccharide units and make up proteoglycans - GAGs are linked to core proteoglycan by linker proteins (GAG portion looks like bottle brushes off of backbone)

Question 11

What gives proteoglycans their biological functions?

Answer 11

THe GAG chain and their linker proteins present with different protein ligands give different roles like coagulation, lipolysis, inflammation, etc.

Question 12

Which type of GAG is non-sulfated?

Answer 12

Hyaluronic acid?

Question 13

Where is hyaluronan found and what is it’s role?

Answer 13

Skin, umbilical cord, eye, synovial fluid of joints, gives lubricating and resistance to compression rles

Question 14

What are some external uses of HA?

Answer 14

Lubrication for eye surgery, tumor marker for progression of breast and prostate cancer, wound healing scaffolding, reduce pain in osteoarthritis by lubrication, anti adhesive product, and fillers in ccosmetic applications

Question 15

What gives ECM tensile strength and elasticity?

Answer 15

Fibrous protein - adhesive glycoproteins

Question 16

What is the major fibrous protein in the ECM? and what do they do?

Answer 16

Collagen - give tensile strength and structural support

Question 17

Where is Collagen I found and how abundant is it?

Answer 17

Skin, tendon, vasculatures, organs, BONE - most abundant >90%

Question 18

Where is Collagen II found?

Answer 18

Cartilage

Question 19

Where is Collagen III found?

Answer 19

Reticulin - reticular fibers or blood vessels

Question 20

Where is Collagen IV found?

Answer 20

Forms bases of cell basement membrane

Question 21

What do most collagen related diseases arise from?

Answer 21

Genetic defects or nutritional deficiencies

Question 22

What does degradation of collagen lead to?

Answer 22

Wrinkles

Question 23

What is osteoporosis?

Answer 23

Not inherited genetically, brought on with age and gender (estrogen deficiency) - reduced levels of collagen in skin and bones

Question 24

What is osteogenesis imperfecta and what causes it?

Answer 24

Cause by a mutation in collagen type I in bone causes fragile bones - can also give scoliosis

Question 25

What is chondrodysplasias?

Answer 25

A skeletal disorder caused by a mutation in type 2 collagen (cartilage) - defect in development of cartilage of long bones giving arrested growth and dwarfism

Question 26

What can help decrease swelling in Rheumatoid arthritis patients?

Answer 26

Organ administration of type II collagen

Question 27

What is the structure of collagen?

Answer 27

A triple alpha helix forms a tropocollogen molecule and these line up to give fibrils

Question 28

What are some medical applications of collagen?

Answer 28

Bone grafting as triple helix makes it strong and does not compromise skeletal structural integrity and is prevented from enzyme breakdown - scaffolds for tissue regeneration and deposition of cells - skin grafts - wound healing processes and cosmetic fillers

Question 29

What do elastins do?

Answer 29

Give elasticity to tissues allowing them to stretch and return to their original pposition

Question 30

Where are elastins found?

Answer 30

Blood vessels, lungs, skin, bladder, ligaments, elastic cartilage

Question 31

What are elastins synthesized by? What degrades them?

Answer 31

Fibroblasts and smooth muscle cells, elastase enzymes degrades activated by fibroblasts and inflammatory cells and MMPs also degrade

Question 32

What are the elastin receptors?

Answer 32

Fibulin-5, Elastonectin, Ficolin, Hucolin

Question 33

What are some diseases associated with elastin?

Answer 33

Some congenital heart defects and hypertension, elastolysis (cutis laxa is the absence of elastin fibers - rare and inherited gives loose folds), williams syndrome, menkes, Marfan's syndrome, and hurler disease

Question 34

How much can elastin stretch and why?

Answer 34

1.5 times their length and snap back to original length because of heavy crosslinking

Question 35

What are examples of adhesive glycoproteins?

Answer 35

Fibronectin, laminin

Question 36

What is the structure of fibronectin? and what is it's cell binding sequence?

Answer 36

Rod like structure with three modules, tripeptide arg-gly-asp are the rgd cell binding sequence - binds to integrin receptors - exists as a dimer in its active form consisting of two nearly identical monomers linked by disulfide bonds

Question 37

How are fibronectins secreted and where do they bind?

Answer 37

Secreted in unfolded, inactive form and then bind to integrins which unfold the fibronectin molecules - where they can form dimers

Question 38

Do fibronectins bind substances besides integrins?

Answer 38

Yes, they are multiadhesive

Question 39

What are two types of fibronectins present in vertebrates?

Answer 39

Insoluble cellular FN - secreted by fibroblasts, major ECM component Soluble plasma FN is a component of blood plasma produced in liver by hepatocytes

Question 40

What is the function of fibronectin?

Answer 40

Cell adhesion, growth, migration and diifferentiation in cell signaling, form blood clots in plasma, structural support and compartmentalization in cellular FN, embryonic development, carcinoma development - alters cell motility so cells get where they don't belong, wound healing

Question 41

What is required for collagen to deposited at wound sites?

Answer 41

FN

Question 42

What are laminins? What is their structure?

Answer 42

A family of glycoproteins that are import to the structural scaffold - major proteins of basal lamina - a heterotrimeric multi-adhesive matrix protein - from networks of web-like structures that resist tensile forces - vital for maintenance and survival of tissues, cell differentiation, migration and adhesion - t structure is advantageous to cross linking

Question 43

What do laminins bind?

Answer 43

Other ECM components like collagens

Question 44

What diseases result from laminin issues?

Answer 44

Congenital muscular dystrophy gives weak muscle, joints and retardation and junctional epidermolysis bullosa (JEB) a skin blistering disease, breast cancer development, neural development - substrate for nerve axon growth