Frassica Lecture Flashcards
what is LRP 5/6 receptor for?
WNT
What accumulates in cystoplasm with WNT binding to LRP5/6?
Beta-catenin—> goes to nuclues and starts intramembranous BONE formation
What can interrupt the WNT pathway?
DDK1 (Dikoft)-1
What does sclerostin do?
Made by osteocytes
- INHIBITS bone formation
- Binds to LRP 5/6 and decrease b-catenin build-up
What does osteoblast produce?
Type I colagent NCProtiens - Ossteonectin - osteopontin - BMP, IGF, TGFbeta
RUNX2, CBFA1 knockout?
Cliedocranial dysplasia
- NO intramembranous BONE therefore NO Clavicles
To formulate bone you need? (mineralize bone)
Ca + Phos + Alk Phosphatase
To resorb bone what pH must be?
<4.0 - Cathespkin K - Collagenase - Acid Phosphase work in this ruffled border RELEASE: Ca/Type I collaged/ NCPs
Type I collagen breakdown procduts?
Hydroxyproline
NTelopeptide
Collagen cross-links
- These indicate HIGH resorption conditions (Pagets Disease, PM Osteoporosis, Multiple Myeloma)
Osteocalcin job?
controls the SIZE of calcium crystal
- Made by osteoblasts
TGF beta and BMP*** from osteoblasts?
- Create a gradient for mesenchymal stem cells at surface
- froms osteoblasts at site left behind from osteoclasts
- COUPLING FACTORS
What are coupling factors
BMP***, TGF-beta
- couple bone resorption with bone formation
Picnodysostosis (osteopetrosis type)
- knock out of Cathepsin K
Most common form of AD Osteopetrosis?
Choloride Channel 7 (cannot make HCl at ruffled broder
What senses calcium levels?
Chief cells of parathyroid gland
- decrease Ca, increase PTH
PTH MOA for increase Calcium?
PTH–> PTHr on osteoblast–> RANKL to RANKR on osteoclasts–> mature osteoclasts (MCSF needs to be present)
PTHrP, Inflammation, MIC1a(from MMyeloma), VitD, Post menapousal osteoporosis, metastatic bone disease, Pagets
- All bind to osteoblasts, makes RANKL
OSTEOCLASTOGENESIS
What does Vit D Do?
- Maintains Calcium LEVELs
- Osteoclastogenesis and gut resorption
Where does OPG Bind and action?
- Binds to RANKL
- Decrease bone resorption
- DENOSUMAB (is MONOCLONAL ANTIBODY TO RANKL)
What two substances does OSTEOCYTE secrete?
- Sclerostin
- FGF 23
FGF23 does what?
- causes you to lose phosphate (decreases serum phosphate)
What are the three conditions that SCLEROSTIN are UPREGULATED?
- Conditions of immobilization
- Spinal chord injury
- Space flight
What are the three conditions that SCLEROSTIN are DOWNREGULATED?
- Exercise
-Load bones
LOADING BONES decreases Sclerostin
X-Linked Phosphatemic Ricketts?
- Missense mutation of PHEX
- Produce FGF 23 excess
- DRIVES phosphate levels LOW- CANT mineralize
ONLY Low serum levels of PHOSPHATE
FGFR23 does what to phosphate?
drops phosphate levels - cant mineralize BONE
- Octreotide SCAN can ID FGFR23
What is histopathology of adamantinoma?
epithelial cells with fibrous stroma
- Treatment is wide resection
- Anterior tibial cortex bubbly lesion
Pagets sarcoma porgession (1%0
Osteosarc>fibrosarc>chondrosarc
bone with mosaic LINES
Mosiac lines in bone disease?
Pagets
virus licke inclusions in osteoclasts
BISPHOSPHONATES
What are verocay bodies located in?
Nuclear Palasades
Shwannoma
- Sometimes associated with nF-2
