Frassica Lecture

Question 1

what is LRP 5/6 receptor for?

Answer 1

WNT

Question 2

What accumulates in cystoplasm with WNT binding to LRP5/6?

Answer 2

Beta-catenin—> goes to nuclues and starts intramembranous BONE formation

Question 3

What can interrupt the WNT pathway?

Answer 3

DDK1 (Dikoft)-1

Question 4

What does sclerostin do?

Answer 4

Made by osteocytes

• INHIBITS bone formation
• Binds to LRP 5/6 and decrease b-catenin build-up

Question 5

What does osteoblast produce?

Answer 5

Type I colagent
NCProtiens
- Ossteonectin
- osteopontin
- BMP, IGF, TGFbeta

Question 6

RUNX2, CBFA1 knockout?

Answer 6

Cliedocranial dysplasia

- NO intramembranous BONE therefore NO Clavicles

Question 7

To formulate bone you need? (mineralize bone)

Answer 7

Ca + Phos + Alk Phosphatase

Question 8

To resorb bone what pH must be?

Answer 8

<4.0
- Cathespkin K
- Collagenase
- Acid Phosphase
work in this ruffled border
RELEASE: Ca/Type I collaged/ NCPs

Question 9

Type I collagen breakdown procduts?

Answer 9

Hydroxyproline
NTelopeptide
Collagen cross-links
- These indicate HIGH resorption conditions (Pagets Disease, PM Osteoporosis, Multiple Myeloma)

Question 10

Osteocalcin job?

Answer 10

controls the SIZE of calcium crystal

- Made by osteoblasts

Question 11

TGF beta and BMP*** from osteoblasts?

Answer 11

• Create a gradient for mesenchymal stem cells at surface
• froms osteoblasts at site left behind from osteoclasts
• COUPLING FACTORS

Question 12

What are coupling factors

Answer 12

BMP***, TGF-beta

- couple bone resorption with bone formation

Question 13

Picnodysostosis (osteopetrosis type)

Answer 13

• knock out of Cathepsin K

Question 14

Most common form of AD Osteopetrosis?

Answer 14

Choloride Channel 7 (cannot make HCl at ruffled broder

Question 15

What senses calcium levels?

Answer 15

Chief cells of parathyroid gland

- decrease Ca, increase PTH

Question 16

PTH MOA for increase Calcium?

Answer 16

PTH–> PTHr on osteoblast–> RANKL to RANKR on osteoclasts–> mature osteoclasts (MCSF needs to be present)

Question 17

PTHrP, Inflammation, MIC1a(from MMyeloma), VitD, Post menapousal osteoporosis, metastatic bone disease, Pagets

Answer 17

• All bind to osteoblasts, makes RANKL

OSTEOCLASTOGENESIS

Question 18

What does Vit D Do?

Answer 18

• Maintains Calcium LEVELs

- Osteoclastogenesis and gut resorption

Question 19

Where does OPG Bind and action?

Answer 19

• Binds to RANKL
• Decrease bone resorption
• DENOSUMAB (is MONOCLONAL ANTIBODY TO RANKL)

Question 20

What two substances does OSTEOCYTE secrete?

Answer 20

• Sclerostin

- FGF 23

Question 21

FGF23 does what?

Answer 21

• causes you to lose phosphate (decreases serum phosphate)

Question 22

What are the three conditions that SCLEROSTIN are UPREGULATED?

Answer 22

• Conditions of immobilization
• Spinal chord injury
• Space flight

Question 23

What are the three conditions that SCLEROSTIN are DOWNREGULATED?

Answer 23

• Exercise
  -Load bones
  LOADING BONES decreases Sclerostin

Question 24

X-Linked Phosphatemic Ricketts?

Answer 24

• Missense mutation of PHEX
• Produce FGF 23 excess
• DRIVES phosphate levels LOW- CANT mineralize
  ONLY Low serum levels of PHOSPHATE

Question 25

FGFR23 does what to phosphate?

Answer 25

drops phosphate levels - cant mineralize BONE | - Octreotide SCAN can ID FGFR23

Question 26

What is histopathology of adamantinoma?

Answer 26

epithelial cells with fibrous stroma - Treatment is wide resection - Anterior tibial cortex bubbly lesion

Question 27

Pagets sarcoma porgession (1%0

Answer 27

Osteosarc>fibrosarc>chondrosarc | bone with mosaic LINES

Question 28

Mosiac lines in bone disease?

Answer 28

Pagets virus licke inclusions in osteoclasts BISPHOSPHONATES

Question 29

What are verocay bodies located in? | Nuclear Palasades

Answer 29

Shwannoma | - Sometimes associated with nF-2