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