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68 Cards in this Set

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2 Ways that bone develops:
1. Intramembranous
2. Endochondral
What forms from intramembranous ossification?
Flat bones
What forms from endochondral ossification?
Long bones
How does Intramembranous ossification proceed in general?
Bone forms in ossification centers.
What begins the ossification center development?
Mesenchyme condensation
What does that ossification center allow?
Osteoblasts can secrete osteoid onto it.
What happens to the osteoid that osteoblasts secrete onto the ossification center?
It calcifies and incorporates osteocytes into individual lacunae.
What bone forming is an example of intramembranous ossification?
Filling in the fontanelles of the calvarium in neonates.
How does Endochondral ossification proceed in general?
Osteoblasts deposit osteoid onto an already existing template of hyaline cartilage.
What is the first step in Endochondral ossification?
Deposition of a bone collar around the perichondrium of the hyaline cartilage template; forms the future diaphysis.
What happens after forming the bone collar?
The cartilage cells that got surrounded by osteoid hypertrophy and apoptose.
What finishes forming of the diaphysis?
Osteoblasts secrete more bone on the matrix of calcified cartilage; the marrow cavity gets cavitated.
How do the epiphyses form in long bones?
Via the same endochondral ossification that forms the diaphysis. However some hyaline cartilage is retained.
What are the 2 forms in which hyaline cartilage is retained at the epiphysis during endochondral ossification?
1. Epiphyseal plate cartilage
2. Articular cartilage
Why is epiphyseal plate cartilage retained?
So that these long bones can grow in length.
What is the first step in long bones growth lengthwise?
Activation of hyaline epiphyseal cartilages (retained at the epiphyses).
How long do humans retain their hyaline epiphyseal plates?
Until age 20
What also occurs as bones grow in length?
Widening
What 5 zones are recognized during long bone growth in length?
1. Reserve zone
2. Proliferative zone
3. Zone of hypertrophy
4. Zone of calcification
5. Ossification
What is in the Reserve Zone?
Cartilage - maintained as a backup store.
What hormone induces cartilage to form in the reserve zone?
Somatotropin - growth hormone.
What induces the pituitary to express this somatotropin/GH?
Sex steroids - estrogen and testosterone.
What sustains the activity in the PROLIFERATIVE zone?
Somatomedins - Insulin like growth factor
What happens in the Hypertrophy zone?
20% of fractures in children
What type of collagen is in the CALCIFICATION zone?
Type X
What 2 cellular processes occur in the calcification zone?
-Chondrocyte proliferation is inhibited
-Hydroxyapatite formation begins
What feature of the calcification zone makes it easier to identify?
Strong Basophilia
How is ossification initiated in the ossification zone?
By the invasion of OSTEOBLASTS.
What type of collagen do osteoblasts synthesize?
Type I collagen
What color develops due to the collagen type I deposition?
Eosinophilia
What 3 cells are involved in REPAIRING bone, and in what order?
1. Macrophages
2. Chondroblasts
3. osteoblasts
What type of ossification occurs during bone repair?
Both intramembranous and endochondral.
What do Macrophages do during repair?
Remove clots
What do chondroblasts do?
Secrete a CALLUS of hyaline cartilage.
What do the osteoblasts do?
Replace the Cartilaginous callus with a Bony callus.
What has to take place after the bony callus is formed?
Remodeling - to replace the primary bone with secondary.
What do difficult fractures require for complete healing?
Bone Grafts
What is better for bone repair than bone grafts?
Inducing the normal bone repair process
What are 3 approaches to inducing bone repair normally?
1. Implants of BMP7 and BMP2
2. Implants of plasmids
3. Implants of mesenchymal stem cells
What is necessary for implanting / injecting these agents?
Putting it in a natural matrix of collagen type i or plastic polymer.
How often is a new skeleton made?
Every 10 years
What 2 processes occur during bone remodeling?
1. Osteoclasts excavate bone
2. Osteoblasts replace it
What hormone made by fat cells induces the CNS to inhibit bone formation?
Leptin
What is osteopetrosis and what causes it?
Too much dense heavy bone because osteoclasts lack a ruffled border.
What is osteoporosis?
Too much resorption of bone by osteoclsts
What score on a bone mineral densitometry indicates that a subject is at high risk for osteoporosis?
2.5 SD below the mean
What do osteoclasts differentiate from?
Stromal cells
What are stromal cells?
Osteoblasts that are like macrophages.
What induces stromal cells to secrete secretory products?
PTH
What products do osteoblasts intended to become osteoclasts secrete? How does each product affect the differentiation?
1. Rank-L - promotes osteoclast
2. M-CSF - promotes osteoclast
3. OPG - inhibits osteoclast
What does M-CSF do?
Stimulates proliferation of macrophages
What does RANK-L do?
Induces the macrophages that proliferated to differentiate into osteoclasts.
How does OPG (osteoprotegerin) inhibit macrophage differntiation into osteoclasts?
By binding up the RANK-L receptor and preventing it from being bound by RANK-L.
What receptor adheres osteoclasts to bone matrix?
Integrin alpha5-beta3
Why is it good to know all about osteoclasts?
To treat osteoporosis.
Regarding Osteoblasts:
-What inhibits their forming?
-What induces their forming?
Leptin Inhibits osteoblasts
BMP/PTH induce osteoblasts
Regarding Osteoclasts:
-What inhibits their forming?
-What induces their forming?
Calcitonin/OPG inhibit osteoclasts
RANK-L/PTH induce osteoclasts.
How can PTH induce both osteoblasts and osteoclasts?
B/c its action is determined by HOW IT is released.
What type of PTH release stimulates osteoblasts?
Spikes
What type of PTH release stimulates osteoclasts?
Constant
What are 4 important anti-resorptive (antiosteoclast) drugs?
1. Estrogen/testosterone
2. SERMS
3. Bisphosphonates
4. Calcitonin
How does estrogen work?
By inducing osteoclast apoptosis
What are 2 SERMs?
-Reloxifen
-Tamoxifen
What is a major Pro-osteoblast drug?
PTH 1-34 INJECTED IN SPIKES
What is the necessary requirement for anti-resorptive drugs to work?
T-score must not be 2.5 SD below the mean.
What would a Cbfa-1 drug do?
Induce osteoblasts
What would inhibit osteoclasts binding the matrix?
Inhibiting Integrin alpha5-beta3
What would inhibit osteoclasts differentiation?
Osteoprotegerin