Cell Biology of Connective Tissue

Question 1

Connective tissue is composed of […] and […]

Answer 1

Cells

Extracellular Matrix

Question 2

• What does the ECM of connective tissue consist of?
• What is its function?

Answer 2

• Fibrous tissue; Collagen; Glycosylated Proteins
• Provide structure and information abut mechanical environment and intracellular environment

Question 3

Connective tissue is derived from embryonic […]

Answer 3

Mesoderm

Question 4

The ratio of matrix to cells in connective tissue is […]

Answer 4

High

Question 5

What are the fibers found in extracellular matrix of connective tissue?

Answer 5

Collagen

Elastic fibers

Reticular fibers

Question 7

What is the function of connective tissue?

Answer 7

To provide mechanical and structural support by interaction of matrix with cells and organs

Question 8

What tissues are considered “specialized connective tissue”?

Answer 8

• Tendons and ligaments
• Bone
• Cartilage
• Blood
• Hematopoetic tissue
• Adipose tissue

Question 9

What is the function of osteoblasts?

Answer 9

• Synthesize and secrete ECM (osteoid) which contains collagen and noncollagenous proteins
• Express alkaline phosphatase and mineralize osteoid via matrix vesicles
• Regulates bone turnover

Question 10

Answer 10

Question 11

This is an image of the basic multicellular unit. Label all the indicated structures.

Answer 11

Question 12

What does collagen contribute to the material properties of bone?

Answer 12

• Tensile strength
• Bone fracture resistance
• Allows cartilage to recover from compressive forces when loaded
• Allows tendons to resist tensile forces and transmits energy from muscle to bone

Question 13

• What is P1NP?
• What does its serum level reflect?

Answer 13

• Collagen is produced in stages, and its precursor protein has a short signal sequence in the N-terminus region that is removed by proteinases. This is P1NP.
• Because it represents a piece of newly made collagen, this is a marker of synthesis of collagen and bone formation

Question 14

What effect does cross-linking the hydroxyl residues on collagen have on its mechanical properties?

Answer 14

Increases strength of collagen network and increases toughness (resistance to fracture) of bone

Question 15

What are NTX and CTX?

Answer 15

These are fragments of type 1 collagen and they are used clinically to measure the rates of bone resorption

Question 16

What enzyme is responsible for crosslinking hydroxyl groups on collagen fibrils?

Answer 16

Lysyl oxidase

Question 17

Describe the arrangement of collagen fibres in bone.

Answer 17

Parallel in the same plane but perpindicular in adjacent planes, like a sheet of plywood. This makes bones more able to accomodate different types of external forces.

Question 18

What does the mineral phase of bone contribute to the mechanical properties of bone?

Answer 18

Compressive strength

Question 19

What is alkaline phosphatase?

Answer 19

Alkaline phosphatase is an ubiquitous membrane-bound glycoprotein that catalyzes the hydrolysis of phosphate monoesters at basic pH values. This phosphate that is liberated can then be used to produce hydroxyapatite.

Question 20

• What disease results when there is a mutation in tissue non-specific alkaline phosphatase (Liver, kidney and bone ALP)?
• What is the treatment?

Answer 20

• There is insufficient phosphate for mineralization of the skeleton so children born with this mutation will have an unmineralized skeleton.
• This used to be a death sentence, but a TNAP replacement enzyme exists called Strensiq that can be administered to mineralize their skeleton

Question 21

Bone has high […] strength but poor […] strength

Answer 21

Compressive

Tensile

Question 22

The collagen in bone makes it more […] and have a […] elastic modulus and the intrafibrillar cross-linking contributes to […] by […] rather than fracturing

Answer 22

Elastic

Lower

Toughness

Deforming

Question 23

The mineral content of bone makes it […] and have a […] elastic modulus. Bone strength and toughness are […] correlated to bone mineral content. When bone becomes too highly mineralized it can become […].

Answer 23

Stronger

Higher (more stiff)

Positively

Brittle

Question 24

How can you estimate toughness by looking at a stress strain curve?

Answer 24

Area under the curve

Question 25

What changes occur in the mineral and collagen of bone due to aging and osteoporosis?

Answer 25

* Loss of mineralized bone --\> decreased strength and stiffness * Decreased collagen content and cross-linking --\> decreased resistance to fracture and elastic properties

Question 26

* What is osteogenesis imperfecta? * What effect does this disease have on the mechanical properties of bone?

Answer 26

* Mutation in type 1 collagen that results in abnormal cross-linking and as a result abnormal template for bone mineralization * Bone has lower stiffness due to lack of elasticity from collagen and improper mineralization --\> more brittle * Unable to resist deformation * Deficient toughness because collagen cross-links are not mature so there is low fracture resistance and high crack propogation

Question 27

Bone that is [...] from the neutral axis at the center of the bone contributes most to its bending strength.

Answer 27

Farthest

Question 28

A bone's bending strength is proportional to the [...] of its distance from the neutral axis

Answer 28

Fourth power (i.e. radius⁴)

Question 29

Boys develop a larger periosteal perimeter than girls from mid-puberty. Who has stronger bones?

Answer 29

Boys

Question 30

Girls have less periosteal bone growth and more endosteal bone growth. Does this give girls an advantage or disadvantage?

Answer 30

Disadvantage - cortical bone will be closer to neutral axis of long bone and less resistant to bending

Question 31

[...] is the primary proteoglycan of cartilage [...] and [...] are the primary GAGs of cartilage

Answer 31

Aggrecan Chondroitin sulfate and keratin sulfate

Question 32

Do chondrocytes express ALP?

Answer 32

Some do - there are chondrocytes in transitional zones or in calcified regions of cartilage that express ALP in order to mineralize the cartilage to bone

Question 33

Answer 33

Question 34

The [...] defines the biomechanical properties of cartilage

Answer 34

Extracellular matrix

Question 35

What gives cartilage its compressive strength?

Answer 35

Negatively charged and hydrated molecules (water)

Question 36

What allows cartilage to deform in response to load?

Answer 36

Solid matrix of proteoglycans and collagen

Question 37

What part of collagen reduces stress at the boundary of the collagen with bone?

Answer 37

The presence of mineral in the zone of transitional tissue

Question 38

Which is stronger - tendons or ligaments?

Answer 38

Tendons

Question 39

Where are fibrochondrocytes found?

Answer 39

At insertions sites of tendons to bones

Question 40

**Fibrochondrocytes** * [...] differentiated * Location? * What do they secrete? * What important protein and unique do they express?

Answer 40

* Terminally * Sparsely located in lacunae between type 2 collagen fibrils * ECM * ALP

Question 41

What is a tenocyte?

Answer 41

Fibroblast like cell found in rows between collagen fibrils (type of fibrochondrocyte)

Question 42

What is an enthesis?

Answer 42

When a tendon directly inserts into the periosteum of the metaphysis or diaphysis. Composed of dense fibrous tissue.