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72 Cards in this Set

  • Front
  • Back
How are osteons formed?
Remodeling of compact bone (replace old & damaged areas)
How does replacement of trabecular bone usually occur?
Absorption pits (can also be by osteons)
What are the functions of trabeculum?
1. Orientation allows forces in multiple directions
2. Light weight but strong
Osteocytes are connected to other cells by?
Cytoplasmic extensions passing through canaliculi
Which layer of the osteon is the oldest layer?
Outer layer
What is the major protein found in bone matrix?
Type I collagen
How is collagen deposited in bone matrix?
Osteoblasts
Fibers of woven bone are laid in what direction?
Varying directions
Fibers of laminar bone are laid in which direction?
Each layer of fibers are oriented in a different direction
Which proteins are found in bone matrix? (4)
1. Collagen
2. Osteocalcin
3. Osteopontin
4. Osteonectin
What is osteocalcin?
Ca binding protein w/ Gla sequences & is Vitamin K dependent
What types of growth factors are found in bone matrix? (3)
1. TGF-beta
2. IGF-1
3. IGF-2
4. BMPs
Function of growth factor binding proteins?
Store, protect & inhibit/activate growth factor action
What is osteopontin?
Binds osteoclasts
RGD sequence
Binds Ca & collagen
What is osteonectin?
Protein that binds Ca & collagen
Hydroxyapatite makes up what percentage of bone content?
50%
Function of hydroxyapatite in bone matrix?
Supports pressures applied to bone
IGF-1 activates which second messenger pathway?
Tyrosine kinase pathway
What is noggin?
Inhibitor of BMP pathway
What is heterotrophic ossification?
Excessive bone growth following amputation
May occur in spine below spinal injury
How does noggin function?
Inhibits signaling of BMPs by preventing their interaction w/ receptors on cell surface
Structure of noggin is very similar to?
BMP-7
Noggin plays key role in?
Formation of nervous system by inhibiting BMP-4
How is noggin crucial in bone development?
Regulates function of BMPs
Mutation of noggin gene leads to?
Skeletal dysplasias
What cell type has a common precursor w/ osteoclasts?
Monocytes
Where are osteoclasts commonly found?
1. Endosteal surfaces
2. Haversian canals
Where are osteoclasts rarely found?
Periosteal surfaces
Nuclei of osteoclasts?
Large multinucleated (10-20)
Where is the ruffled border of osteoclasts located?
Next to bone surface-- release enzymes & acids
Osteoclasts form what in the bone? (2)
1. Reabsorption pits (Howship's lacuna)
2. Tunnels
Layers of periosteum?
1. Outer layer-- very fibrous
2. Inner layer-- cellular w/ blood vessels, nerves
In what type of bones is inner layer more extensive?
Growing bones
What happens in the BMP 2nd messenger cascade?
BMP binds receptor --> activates Smads (transcription factors) -->Smads activate other TFs and turn on genes
Mutation in Noggin gene that decreases inhibitory effect of noggin on BMP4 causes a disease know as?
Fibrodysplasia ossificans progressiva (FOP)-- heterotrophic osteogenesis
What happens in people w/ FOP?
Excessive bone is formed (primarily in skeletal muscles)-- Osteblasts are formed by BMP4 acting on mesenchymal cells
New bone formation in FOP appears to follow?
Inflammation occurring a specific area of the muscle--> increased action of BMP4 in these areas
How is a tooth bud made? (4)
1. Mix epithelial cells & mesenchymal cells in collagen gel
2. Culture for 5-7 days
3. Extract tooth & allow wound heling
4. Transplant bio-engineered tooth
Most arteries in bone originate from?
Nutrient arteries distributed along endostem
Where are capillaries located in bone?
2 in each erosion canal
Most veins exit where in bone?
Periosteum
What is the osteoblast lineage? (5)
1. Mesenchymal stem cell
2. Early pre-osteoblast
3. Late pre-osteoblast
4. Mature osteoblast or bone lining cell
5. Osteocyte or death by apoptosis
What stimulates differentiation of mesenchymal cell to early pre-osteoblast?
BMPs
What stimulates proliferation & differentiation of early pre-osteoblast to late pre-osteoblast? (2)
1. BMPs
2. IGF-1,2
What stimulates late pre-osteoblast to develop into mature osteoblast or bone lining cell?
IGF-1,2
Osteoblasts have what on outside surface of cells & that are important for what?
Alkaline phosphatase-- important in mineralization
What are the only cell type found within bone matrix?
Osteocytes
Osteocytes cell processes extending in canaliculi are connected to other processes & cells on bone surface by?
Gap junctions
What do both mature osteoblasts & osteocytes have in common?
Do not multiply
What are the functions of osteocytes? (3)
1. Help maintain bone
2. Sense application of periodic pressure
3. Transport Ca through canaliculi into circulation (osteocytic osteolysis)
What is a quick way to increase ECF Ca?
Osteocytic osteolysis
What surrounds ruffled border of osteoclasts?
Clear zone (free of organelles)
How does clear zone attach to bone?
Intercellular actin filaments in clear zone of cytoskeleton of osteoclasts are attached to integrins which are attached to extracellular collagen by attachment proteins
What types of attachment proteins attach integrins to collagen?
Proteins w/ RGD sequence (fibronectin or vitronectin)
What releases osteoclasts from extracellular matrix?
Phosphorylation of integrin receptor by kinase
Activators of osteoclasts? (3)
1. PTH
2. 1,25 D3
3. ODF (RANK-L)
Inhibitors of osteoclasts? (2)
1. Calcitonin
2. OPG (osteoprotegrin)
Steps of osteoclast differentiation? (5)
1. Bone marrow stem cell
2. Pre-monocyte/osteoclast
3. Early pre-osteoclast
4. Late pre-osteoclast
5. Osteoclast
What promotes fusion of pre-osteoclasts?
PTH & 1,25 D3
ODF is produced by?
pre-osteoclasts
What is ODF?
Juxtacrine factor attached to outside of pre-osteoclasts
ODG (osteoprotegrin) is produced by?
Osteoblast lineage cell
What happens when ODG binds ODF?
Blocks action of ODF & inhibits osteoclast formation
How is bone resorbed by osteoclasts? (3)
1. Osteoclasts form resorption pits (Howship's lacuna)
2. H+ dissolve bone mineral & provide proper pH for enzymes
3. Enzymes degrade ECM
How is compact bone remodeled? (3)
1. Erosion canal formed by osteoclasts
2. Osteoblasts fill canal w/ new bone
3. New osteon formed w/ in compact bone
How are H+ ions secreted into area of bone resorption?
Primary active transporters (w/ Cl) in membrane of ruffled border
Which class of primary active transporters are found on osteoclast's plasma membrane?
V-class
What is bone coupling & what stimulates it?
During bone remodeling, the bone removed is replaced by the same amount of bone-- release of growth factors that were bound to proteins stimulate replacement
What is osteopetrosis & what causes it?
Very dense bone -- when osteoclasts don't function
Deficiency in carbonic anhydrase II causes? (2)
1. Osteopetrosis
2. Renal tubular acidosis
Usual causes of bone loss? (3)
1. Aging
2. Decreased estrogen & testosterone
3. Lack of exercise
Increased bone loss due to increased? (6)
1. Glucocorticoids
2. Thryoxine
3. Alcoholism
4. Removal of part or all of stomach or GI diseases
5. Hypercalciuria
6. Smoking