Connective Tissue/Bone

Question 1

Structure of Collagen?

Answer 1

Glycine every 3rd AA
Hydroxyprolines or proline => cross-helix H bonding
Hydroxylysines=> corss lins between collagen

Triple helix
End/tail: clipped by procollagen peptidase
Assembled into fibrils in ECF

Question 2

Precursor of all proteins?

Answer 2

mRNA

Question 3

Steps of collagen synthesis?

Answer 3

mRNA => hydroxylation in ER/ Vit C dependent => attachment of soluble galactosyl/sugars to hydroxylsyl residues

Question 4

Types of collagen and their role in disease?

Answer 4

Type I: skin/tendons/ligaments => OI types I-IV, osteoporosis

Type II: hyaline cartilage/vitreous humor/eye => Types II/XI collagenopathies

Type III: skin/muscle/intestine/glands => Ehlers-Danlos syndrome, aneurysms

Type IV: forms sheets, not fibers => HANAC, familial benign heaturia, Goddpasture’s syndrome

Question 5

3 dominant types of fibers in CT?

Answer 5

Collagenous
Elastic
Reticular fibers

Question 6

Characteristics of different fiber types?

Answer 6

Collageneous: composed of collagen/fibrils 1/4 of protein in body

Reticular: type III in liver/muscle/bone marrow/lymph => supportive

Elastic: microfibrils => irregular/random coils => desmosine cross links => strength/elasticity

Question 7

Inorganic vs organic bone matrix components?

Answer 7

Inorganic: from calcium hydroxyapatite

Organic: type I collagen = osteoid and growth factors = ground substance

Question 8

Know pic Pg 22 and

Answer 8

31

Question 9

Osteoblasts vs -clasts vs -cytes?

Answer 9

Osteoblast: produce bone/inorganic/organic/ground substance

Osteoclasts: modified monocyte/macrophage => resorption/cleavage of bone

Osteocytes: former osteoblasts trapped in organic bone, link via canaliculi/gap junctions

Question 10

Steps of transforming growth factor-beta signaling?

Answer 10

Changes gene activity

Two TGF-beta proteins form dimer (cysteine knot)
=> interacts with T-beta-R-II => recruit T-beta-R-I => T-beta-R-II conformational change => phosphorylation of R-I => activate SARA => SMAD4/RSMAD

Question 11

Osteoblast secrete? Produce

Answer 11

Type I collagen/Gp/proteoglycans

Ground substance composed of GAG, Gps

Cytokine M-CSF =>promote osteoclast growth/diff

Question 12

Glycoproteins secreted by osteoblasts?

Answer 12

Osteocalcin
Osteonectin => mineralization process
Osteopontin => increased by calcitriol/Vit D3

Question 13

Positive and negative regulation of osteoclasts?

Answer 13

Positive: RANKL/M-CSF
Receptor activator of nuclear factor kappa B Ligand

Negative: OPG by inhibiting RANK/NF-kB
Osteoprotegerin

Question 14

Role of podosome?

Answer 14

Osteoclast adhesion mediating osteoclast-ECF interaction

Actin rich, attach to integrin receptor

Question 15

Which chemical of osteoclasts degrades collagen matrix via selective cleavage of collagen?

Answer 15

Cathepsins like cathepsin K

Question 16

Enzymes involved in break down of in/organic matrix by osteoclasts?

Answer 16

Asparate protease

Matrix metalloprotease

Question 17

Most abundant bone cell?

Answer 17

Osteocyte

Question 18

Bone growth regulation? Balance depends on? Hormones?

Answer 18

Remodeling/break down dependent on:
FGF
PDGF
TGF-beta
BMPs
Polypeptide growth hormone (from pituitary)

Androgen/estrogen => promote osteoblast activity => promotes OPG => inhibits RANK

PTH

Question 19

Bone resorption control?

Answer 19

Increased:
PTH
Vit D -> IL-6
M-CSF (also inhibits OPG)

Question 20

Difference intramembraneous ossification vs endochondral ossification?

Answer 20

Intramembranous: skull, and during repair of fractures => direct bone deposition into CT

Endochondral: formation of all other long bones/flat/irregular/ continued growth during childhood/ fracture repair => starts with hyaline cartilage

Question 21

3 phases of bone healing?

Answer 21

Reactive: minutes->days
Clot forms

Reparative phase: days-weeks

Remodeling: weeks-months
Selective resorption/redeposition until final compact bone matrix is produced

Question 22

Relationship of PTH and calcitonin?

Answer 22

Antagonists

PTH increases Ca in serum:
PTH => increases reabsorption of Ca, Vit D in intestine/kidney
Bone: increase RANK => demineralization

Calcitonin: reduces blood Ca
Calcitonin => decreases Ca reabsorption, inhibits mineralization
Also secreted in response to gastrin
=> Gq receptor

Question 23

Regulation of Ca/D ?

Answer 23

Ca in GI => absorption stimulated via 1,25 (OH)2D into blood and also stimulates mineralization

E2 stimulates mineralization

PTH stimulates reabsorption of Ca and mineralization

Calcitonin inhibits reabsorption of Ca and mineralization