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