BS - Bone, Cartilage, Molecular Biology, &c Flashcards Preview

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Flashcards in BS - Bone, Cartilage, Molecular Biology, &c Deck (66):
1

Signal through tyrosine kinase receptors

Fibroblast growth factors, insulin-like growth factors, and platelet-derived growth factors

2

Parathyroid hormone receptor SIGNALLING MECHANISM

adenylyl cyclase/G-alpha stimulatory protein/cAMP/protein kinase A

3

TGF-ß SIGNALLING AND EFFECT osteoblasts

stimulates osteoblasts to synthesize collagen and primarily signal through serine/threonine kinase receptors

4

BMP SIGNALLING MECHANISM

BMPs target undifferentiated mesenchymal cells and signal through serine/threonine kinase receptors

 

SMADS are primary intracellular signaling mediator for bone morphogenetic protein 

5

IGF-II SIGNALLING MECHANISM

tyrosine kinase receptors

6

Osteoclast ACTIVATING MOLECULES (7)

RANKL, PTH, IL1, 1,25 Vitamin D

 

prostaglandin E2, IL-6, MIP-1A

7

Osteoclast INHIBITING MOLECULES (6)

OPG, calcitonin (osteoclast receptor), estrogen, TGFbeta, IL-10

DENOSUMAB (monoclonal ab binds to RANKL like OPG)

8

Type 1 collagen breakdown marker

hydroxy-proline

9

BMP3 features (3)

Antagonizes BMP2

Most abundant BMP in demineralized bone matrix

increases chondrogenic markers

10

Factor that couples bone resorption and formation

TGFß

- signals osteoblasts to make bone

- acid pH activates TGFß family

- negative effect on epithelial cell proliferation

11

TGFß signalling pathway

Type I/II receptor --> SMAD4

- SMURFS regulate and breakdown SMADs

12

TGFß effects on cartilage

chondrocyte hypertrophy

(TGFß knockout mice --> arthritis)

13

Name 2 adhesive proteins and their function

Fibronectin - osteoblast adhesion to bone and survival

Vitronectin - osteoclast adhesion to bone (alpha-v/neta-3 integrin receptor)

14

Osteoblast markers (5) 

osteocalcin (most specific)

alk phos

PTH receptor

osteonectin

osteopontin

15

osteoclast markers (4)

TRAP (tartrate resistant acid phosphatase)

calcitonin receptor

RANK

alpha-v/beta-e integrin receptor

16

LRP5 signalling pathway and effects

Wnt/Frizzled transduction pathway

regulates osteoblast activity

Loss function = poor bone mass "osteoporosis-pseudoglioma"

Gain function - very high boner mass

17

osteoporosis features (3)

- T score < 2.5 std dev (below peak bone mass)

- normal mineralization

- abnormal microarchitecture (anisotropy increased, porosity increased)

18

Contraindications PTH therapy (4)

- Paget's/post irradiation (risk for osteosarc)

- open physes

- hyperparathyroidism

- metastatic bone disease

19

Trabecular bone features (3)

- maximum thickness plates and rods 200 micron

- blood supply = diffusion

- 30-90% porosity

20

Hydroxyapatite molecular formula

Ca10(PO4)6(OH)2

21

Q image thumb

- Stone man syndrome, aka "fibrodysplasia ossificans progressiva"

- activating mutation in ACVR1 (BMP receptor)

22

Schwartzman's reaction

systemic response to bacterial endotoxins --> DIC, fat embolism, thrombosis

May cause OSTEONECROSIS

23

Names and mechanism of nitrogen containing bisphosphonates

alendronate, risedronate, pamidronate, zolendronate

- inhibit mevalonate (cholesterol pathway)

- inhibits osteoclast farnesyl pyrophosphate synthase enzyme

-prevent post-translational prenylation of GTP-binding proteins

- inhibits ruffled border and microtubules

24

Names and mechanism of NON-nitrogen containing bisphosphonates

tiludronate, clodronate, etidronate

- produce toxic analogs of ATP

25

Bisphosponate indications (7)

osteogenesis imperfecta

osteoporosis


metastatic bone disease
multiple myeloma
paget's disease
polyostotic fibrous dysplasia


early stage avascular necrosis (precollapse)
 

26

bisphosphonate contraindications (2)

severe renal disease

following lumbar fusion

27

c-fos

Leucine zipper type transcription factor

overexpression in transgenic mice causes chondrosarcomas

28

leucine zipper transcription factors

c-fos

c-jun (AP-1)

NFkB

29

Zinc finger transcription factors

Vitamin D receptor

Thyroid hormone receptor

Retinoid receptor

30

MyoD

Helix-loop-helix transciption factor regulates myoblast differentiation

31

Bone characterized by slow turnover rate and high Young's modulus

cortical bone (macroscopic structural classification)

32

Bone with lower Young's modulus (more elastic) and 
high turnover to remodel according to stress across the bone

Cancellous bone (macroscopic structural classification)

33

woven bone characteristics

woven = "primary bone" microscopic classification

immature (fracture callus) or pathologic bone
not stress oriented
less mineralized, smaller crystals

more osteocytes per unit of volume
higher rate of turnover

weaker and more flexible than lamellar bone

A image thumb
34

lamellar bone characteristics

lamellar = "secondary bone"

created by remodeling woven bone

also periosteal new bone


organized and stress oriented
stronger and less flexible than woven bone

A image thumb
35

2 main promoters for initial bone mineralization (nucleation)

biglycan (associated with TGFß)

bone sialoprotein 2

36

BMP4 (2 points)

overexpression = fibrodysplasia ossificans progressiva

 

crucial for apoptosis in formation of digital web spaces

37

BMP that does not exhibit osteoinductive activity 

BMP3

38

4 BMPs all exhibit osteoinductive activity

2, 4, 6, 7

(PRIMARILY 2, 7)

Remember BMP7 aka "OP1"

39

BMP's found in hypertrophic cartilage, promotes cartilage differentiation and the enchondral pathway 

BMP 6, 7

40

3 genes implicated in osteoporosis development

COL1A1

vitamin D receptor

LRP5 (LDL receptor related protein)

41

DNA features (5)

bases are thymine, adenine, guanine, and cytosine (TAGC)

double-stranded only

hydrogen group instead of a hydroxyl group at the 2’ position in the ribose.

located in the nucleus only

helix is of B-Form

42

RNA features

bases are uracil, adenine, guanine, and cytosine (UAGC)

may be either single or double-stranded

hydroxyl group at the 2’ position in the ribose

found in the nucleus and the cytoplasm in the form of mRNA

helix geometry is of A-Form

43

cement lines

found only in secondary bone due to remodling

1-5 micron thick

low in collagen content 

may fuction as crack arrestor

44

Perlecan proteoglycan

regulates formation and activity of osteoblasts

45

Decorin

proteoglycan with role in collagen fibril assembly (tendon)

46

osteogenesis imperfecta mutation

substitution of glycine (to bulkier AA's) in the procollagen mollecule

47

collagen structure

two alpha1 chains
one alpha2 chain 

A image thumb
48

collagen synthesis

A image thumb
49

Type III collagen

5% dry weight tendons

important in inflammation phase of tendon healing (replaced to type 1 collagen in remodeling)

site of soft tissue attachments, artery walls, skin

Ehlers-Danlos syndrome, Dupuytren's association

50

 Type II collagen

Hyaline cartilage

nucleus pulposus of intervertebral disks

51

Type IV collagen

basement membranes (think renal diseases if mutation)

 

least affected by the collagenase compounds utilized in
collagenase clostridium histolyticum injection for
the treatment of Dupuytren’s contracture

52

Type X collagen

hypertrophic and mineralizing cartilage

- deep calcified layer of cartilage

- produced only by hypertrophic chondrocytes during enchondral ossification (growth plate, fracture callus, heterotopic ossification)

- increased in early arthritis

-Schmid metaphyseal chondrodysplasia

53

 Cathepsin K

enzyme produced and released by osteoclasts at the ruffled border that functions to resorb bone

54

function of the core binding factor alpha-1 (Cbfa1/Runx2)

key transcription factor associated with osteoblast differentiation, skeletal morphogenesis, and acts as a scaffold for nucleic acids and regulatory factors involved in skeletal gene expression

55

PDGF role in fracture healing

chemotactic and attracts inflammatory cells to the fracture site and is important in early fracture healing, especially the hematoma formation

56

Final differentiation for mesenchymal stem cells (6)

 muscle, fat (adipocyte), tendon (fibroblast), bone (osteoblast), cartilage (chondrocyte), and the marrow stromal cells

 

NOT OSTEOCLAST (Monocyte lineage)

57

Osteonectin

glycoprotein that binds calcium

58

Which of the following growth factors binds and activates the lipoprotein receptor-related
protein 5/6 (LRP5/6) during bone development?

Wnt protein

Wnts are a large family of secreted proteins (19 different members in the human genome) that transduce their signal through several pathways. The most studied of
these pathways is the Wntlbeta-catenin pathway, in which Wnt protein binds to the LRP5/6 receptor at the cell surface and activates an intracellular cascade. This cascade leads to translocation of beta-cat en in into the nucleus to activate transcription of genes that control
osteoblast differentiation.

59

An osteoprogenitor cell is expected to commit to a bone lineage in the presence of what transcription factor? 

Runx2

60

Transcription factors for cell lineages of interest

osteoblast - Runx2/Osx

adipocyte - PPARy

myoblast - MyoD

chondroblast - Sox 9

61

function of carbonic anhydrase in bone

generate hydrogen ions at the ruffled border

underlying hydroxyapatite is solubilized in the low pH and calcium ions are released

62

Southern blotting

DNA sequence

63

Northern blotting

RNA sequence

64

Western blotting

identifies protein

65

Polymerase chain reaction (PCR)

DNA → DNA

66

Reverse transcription polymerase chain reaction (RT-PCR)

RNA →DNA