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ABOS > BS - Bone, Cartilage, Molecular Biology, &c > Flashcards

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

1
Q

Signal through tyrosine kinase receptors

A

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

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2
Q

Parathyroid hormone receptor SIGNALLING MECHANISM

A

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

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3
Q

TGF-ß SIGNALLING AND EFFECT osteoblasts

A

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

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4
Q

BMP SIGNALLING MECHANISM

A

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

SMADS are primary intracellular signaling mediator for bone morphogenetic protein

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5
Q

IGF-II SIGNALLING MECHANISM

A

tyrosine kinase receptors

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6
Q

Osteoclast ACTIVATING MOLECULES (7)

A

RANKL, PTH, IL1, 1,25 Vitamin D

prostaglandin E2, IL-6, MIP-1A

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7
Q

Osteoclast INHIBITING MOLECULES (6)

A

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

DENOSUMAB (monoclonal ab binds to RANKL like OPG)

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8
Q

Type 1 collagen breakdown marker

A

hydroxy-proline

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9
Q

BMP3 features (3)

A

Antagonizes BMP2

Most abundant BMP in demineralized bone matrix

increases chondrogenic markers

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10
Q

Factor that couples bone resorption and formation

A

TGFß

  • signals osteoblasts to make bone
  • acid pH activates TGFß family
  • negative effect on epithelial cell proliferation
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11
Q

TGFß signalling pathway

A

Type I/II receptor –> SMAD4

  • SMURFS regulate and breakdown SMADs
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12
Q

TGFß effects on cartilage

A

chondrocyte hypertrophy

(TGFß knockout mice –> arthritis)

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13
Q

Name 2 adhesive proteins and their function

A

Fibronectin - osteoblast adhesion to bone and survival

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

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14
Q

Osteoblast markers (5)

A

osteocalcin (most specific)

alk phos

PTH receptor

osteonectin

osteopontin

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15
Q

osteoclast markers (4)

A

TRAP (tartrate resistant acid phosphatase)

calcitonin receptor

RANK

alpha-v/beta-e integrin receptor

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16
Q

LRP5 signalling pathway and effects

A

Wnt/Frizzled transduction pathway

regulates osteoblast activity

Loss function = poor bone mass “osteoporosis-pseudoglioma”

Gain function - very high boner mass

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17
Q

osteoporosis features (3)

A
  • T score < 2.5 std dev (below peak bone mass)
  • normal mineralization
  • abnormal microarchitecture (anisotropy increased, porosity increased)
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18
Q

Contraindications PTH therapy (4)

A
  • Paget’s/post irradiation (risk for osteosarc)
  • open physes
  • hyperparathyroidism
  • metastatic bone disease
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19
Q

Trabecular bone features (3)

A
  • maximum thickness plates and rods 200 micron
  • blood supply = diffusion
  • 30-90% porosity
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20
Q

Hydroxyapatite molecular formula

A

Ca10(PO4)6(OH)2

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21
Q
A
  • Stone man syndrome, aka “fibrodysplasia ossificans progressiva”
  • activating mutation in ACVR1 (BMP receptor)
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22
Q

Schwartzman’s reaction

A

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

May cause OSTEONECROSIS

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23
Q

Names and mechanism of nitrogen containing bisphosphonates

A

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
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24
Q

Names and mechanism of NON-nitrogen containing bisphosphonates

A

tiludronate, clodronate, etidronate

  • produce toxic analogs of ATP
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25
Q

Bisphosponate indications (7)

A

osteogenesis imperfecta

osteoporosis

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

early stage avascular necrosis (precollapse)

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26
Q

bisphosphonate contraindications (2)

A

severe renal disease

following lumbar fusion

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27
Q

c-fos

A

Leucine zipper type transcription factor

overexpression in transgenic mice causes chondrosarcomas

28
Q

leucine zipper transcription factors

A

c-fos

c-jun (AP-1)

NFkB

29
Q

Zinc finger transcription factors

A

Vitamin D receptor

Thyroid hormone receptor

Retinoid receptor

30
Q

MyoD

A

Helix-loop-helix transciption factor regulates myoblast differentiation

31
Q

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

A

cortical bone (macroscopic structural classification)

32
Q

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

A

Cancellous bone (macroscopic structural classification)

33
Q

woven bone characteristics

A

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

34
Q

lamellar bone characteristics

A

lamellar = “secondary bone”

created by remodeling woven bone

also periosteal new bone

organized and stress oriented
stronger and less flexible than woven bone

35
Q

2 main promoters for initial bone mineralization (nucleation)

A

biglycan (associated with TGFß)

bone sialoprotein 2

36
Q

BMP4 (2 points)

A

overexpression = fibrodysplasia ossificans progressiva

crucial for apoptosis in formation of digital web spaces

37
Q

BMP that does not exhibit osteoinductive activity

A

BMP3

38
Q

4 BMPs all exhibit osteoinductive activity

A

2, 4, 6, 7

(PRIMARILY 2, 7)

Remember BMP7 aka “OP1”

39
Q

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

A

BMP 6, 7

40
Q

3 genes implicated in osteoporosis development

A

COL1A1

vitamin D receptor

LRP5 (LDL receptor related protein)

41
Q

DNA features (5)

A

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
Q

RNA features

A

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
Q

cement lines

A

found only in secondary bone due to remodling

1-5 micron thick

low in collagen content

may fuction as crack arrestor

44
Q

Perlecan proteoglycan

A

regulates formation and activity of osteoblasts

45
Q

Decorin

A

proteoglycan with role in collagen fibril assembly (tendon)

46
Q

osteogenesis imperfecta mutation

A

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

47
Q

collagen structure

A

two alpha1 chains
one alpha2 chain

48
Q

collagen synthesis

A
49
Q

Type III collagen

A

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
Q

Type II collagen

A

Hyaline cartilage

nucleus pulposus of intervertebral disks

51
Q

Type IV collagen

A

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
Q

Type X collagen

A

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
Q

Cathepsin K

A

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

54
Q

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

A

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
Q

PDGF role in fracture healing

A

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

56
Q

Final differentiation for mesenchymal stem cells (6)

A

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

NOT OSTEOCLAST (Monocyte lineage)

57
Q

Osteonectin

A

glycoprotein that binds calcium

58
Q

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

A

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
Q

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

A

Runx2

60
Q

Transcription factors for cell lineages of interest

A

osteoblast - Runx2/Osx

adipocyte - PPARy

myoblast - MyoD

chondroblast - Sox 9

61
Q

function of carbonic anhydrase in bone

A

generate hydrogen ions at the ruffled border

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

62
Q

Southern blotting

A

DNA sequence

63
Q

Northern blotting

A

RNA sequence

64
Q

Western blotting

A

identifies protein

65
Q

Polymerase chain reaction (PCR)

A

DNA → DNA

66
Q

Reverse transcription polymerase chain reaction (RT-PCR)

A

RNA →DNA

ABOS (19 decks)

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