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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
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 ## Footnote 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
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
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
48
collagen synthesis
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 ## Footnote - 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 ## Footnote 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

ABOS (19 decks)

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