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A464-Test 3
lecture 17
46
Anatomy
Undergraduate 4
03/29/2011

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Term
bone functions are mediated by relationships between the two tissue types: ___ and ____
Definition
cartilage and bone
Term
two major types of bone
Definition
1. flat bones
2. long bones
Term
flat bones
Definition
parietal bones of skull mandible and maxillae
Term
long bones
Definition
endochondral bones of the rest of the body (long bones and vertebrae)
Term
flat or intramembranous bone formation (4 steps)
Definition
1. condensation of mesenchymal cells 2. directly differentiate into osteoblasts 3. bone matrix produced from many points in condensed mesenchyme and ultimately fused into bone 4. minimal bone marrow cavity results from inner regions that don't form bone
Term
long or endochondral bone formation (7 steps)
Definition
1. Condensation of mesenchyme-differentiation to cartilage (hyaline) forms a small cartilagenous model of the bone.

2. In perichondrium of the diaphysis, bone collar forms.- perichondrial fibroblasts differentiate directly into bone forming cells (similar to what happens in intramembraneous bone formation .

3. Cartilage under bone collar becomes hypertrophic makes type X collagen and this collects precipitated hydroxyapatite Ca10(PO4)6 (OH)2

4. Formation of the primary ossification center
a) Endothelial cells invade mineralized cartilage of the diaphysis leading to blood vessel growth (angiogenesis) .
b) Osteoclasts come in with blood supply bone and degrade calcified cartilage
c) Osteoprogenitor cells come in with blood supply, differentiate to osteoblasts, and begin forming bone on the remodeled calcified cartilage surfaces

5. Secondary ossification center formed in epiphysis by a series of events similar to those that occur in the primary ossification center.

6. Growth plate formation- between the bone that forms from the primary and secondary ossification events a strip of cartilage remains that is called a growth plate.

7. Articular cartilage formation- a strip of cartilage is maintained at the outer edge of the epiphysis
Term
cells of the growth plate, overall structure
Definition
composed of rows of chondrocytes undergoing an ordered process of differentiation and subsequent destruction
Term
zones of growth plate
Definition
parallel regions where chondrocytes are in a similar differentiation state
1. resting
2. proliferating
3/4. hypertrophic, apoptotic
5. ossification
Term
resting zone
Definition
committed stem cells not dividing (look for cells with small nuclei above proliferating zone, usually one cell per lacunae)
Term
proliferating zone
Definition
transiently amplifying cells of cartilage, rapidly dividing synthesizing some matrix (look for stacks of 3 to 5 cells in a lacunae, nuclei appear flat-looking bands)
Term
hypertrophic zone
Definition
terminally differentiated cells synthesize a unique cartilage matrix (type X collagen) that becomes mineralized. ultimately, these cells die by apoptosis (look for big empty cells at bottom of zone)
Term
ossification
Definition
messy region where angiogenesis, osteoclast-mediated resorption of mineralized cartilage and osteoblast mediated bone formation on islands of remodeled mineralized cartilage occurs simultaneously
Term
within the growth plate, proliferation rate = ___?
Definition
chondrocyte death
Term
within the growth plate, does the growth plate cartilage change or stay the same size?
Definition
same size
Term
new bone growth occurs as ____ _____
Definition
hypertrophic cartilage
Term
hypertrophic cartilage is converted to _____
Definition
bone; this is where length is added to bones
Term
when does bone growth stop?
Definition
when the growth plate cartilage disappears
Term
do adults have growth plates in their long bones?
Definition
no
Term
what plays a role in the closing of the growth plate?
Definition
increased estrogen levels
Term
indian hedgehog
Definition
a growth factor that is expressed by the hypertrophic chondrocytes. it drives chondrocytes to differentiate and hypertrophy (terminal differentiation, synthesize type X collagen mineralization/calcification, and apoptosis of chondrocytes)
Term
PTHrP
Definition
growth factor that is expressed in the region between the resting chondrocytes and the bone of the epiphysis. there is a concentration gradient of PTHrP formed within the proliferating zone of the cartilage matrix
Term
PTHrP receptor
Definition
found in the proliferating zone and some of the prehypertrophic chondrocytes of the growth plate
Term
stimulation of PTH/PTHrP receptor does what?
Definition
blocks differentiation of proliferating to hypertrophic chondrocytes. this ensures there is enough proliferating chondrocytes to maintain the growth plate.
Term
synovial joint/diathroses
Definition
links two bone and permits free bone movement between the bones
Term
ligaments
Definition
tough connective tissue (fibrocartilage in some segments that are connected to bones) and that link the bone
Term
capsule
Definition
specialized connective tissue that is continuous with ligaments, encloses the ends of the bone
Term
synovium/synovial membrane
Definition
lining of cavity made up of macrophage-like cells, underlying this layer are active fibroblasts and fenestrated capillaries that play a major role in producing synovial fluid.
Term
synovial fluid
Definition
plasma that is also high in concentration of hyaluronic acid and serves as a medium of exchange for nutrients and waste products for the articular cartilage
Term
articular cavity/joint cavity
Definition
space enclosed by capsule filled with synovial fluid
Term
articular cartilage
Definition
the layer of cartilage that covers long bones. required for smooth movement of bone against bone in the joint
Term
matrix of articular cartilage
Definition
generally similar to hyaline cartilage but has a small amount of type I collagen fibers. does not have a pericondrium. now think it is a specialized type of cartilage, distinct from other types of cartilage.
Term
example of non-synovial joint
Definition
intervertebral disk structure that is bounded by bone (vertebrae) and ligaments. does not provide much movement
Term
anulus fibrosis
Definition
disc of fibrocartilage that separates vertebrae
Term
nucleus pulposus
Definition
fluid-filled center of the disk that is surrounded by the anulus fibrosis
Term
slipped disc
Definition
occurs when nucleus pulposus is extruded through weakened fibrocartilage
Term
why is repair of cartilage bad?
Definition
it lacks vascular tissue. repair is poor in tissues that lack blood vessels. much of repair in body is downstream of blood clots that form from platelets
Term
repair of cartilage when perichondrium is present
Definition
damaged cartilage is invaded by precursor cells from the perichondrium that differentiate into chondroblasts synthesize matrix and repair cartilage, however, cartilage matrix is not laid down appropriatelyy. the resulting cartilage that is produced is often defective
Term
repair of cartilage with no perichondrium
Definition
repair is very poor b/c lack of precursor/stem cells. examples: ligaments, articular cartilages, and intervertebral discs.
Term
repair of bone
Definition
1. breakage of calcified bone matrix results in the breakage of vasculature. this causes release of platelets and formation of a blood clot around the broken area.
2. the blood clot is invaded by fibroblasts/mesenchymal precursor cells that produce a CT to rejoin broken bone
3. within the connective tissue, endochondral and intermembranous bone formation occurs and a bone callus forms (primary bone)
4. ultimately primary bone remodeled to secondary bone
Term
osteoarthritis
Definition
a disease of articular cartilages
-affecting more than 20 million Americans
-disease of cartilage degeneration
-chronic pain in specific joints of the hands, feet and those that play a key role in weight bearing
-usually articular cartilage is lost fom the joint and bone and is exposed
-changes in chondrocytes composing articular cartilage occur before the loss of tissue
-normally articular chondrocytes are very inactive (not proliferating or differentiating, making very small amts of matrix)
-chondrocytes in patients with early osteoarthritis often undergo hypertrophic differentiation making type X collagen and undergoing apoptosis
-calcified cartilage is converted to bone, ruining smooth surface that permits normal joint function
-at this point there is no treatment of osteoarthritis beyond management of pain
-severe osteoarthritis is replaced with an artificial joint
Term
two factors contributing to osteoarthritis
Definition
-elderly
-more common in joints that have experienced trauma or extreme use
Term
where in the body are articular cartilages found?
Definition
lining the bone in synovial joints
Term
what type of cartilage cells are present in articular cartilages affected by osteoarthritis?
Definition
hypertrophic chondrocytes
Term
which cell fate do hypertrophic chondrocytes undergo?
Definition
they represent the terminal differentiated step of the growth plate chondrocyte lineage and they undergo apoptosis as the last part of the differentation process
Term
what unique form of collagen is made by hypertrophic chondrocytes?
Definition
type X collagen
Term
what replaces articular cartilage in severe cases of osteoarthritis?
Definition
bone
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