Bone Formation and Growth Hormone Flashcards
0
Q
Where does REABSORPTION occur?
A
Kidneys (tube–>blood)
1
Q
Where does ABSORPTION occur?
A
Intestines
2
Q
Where does RESORBTION occur?
A
Bone
3
Q
What are two classifications of bone formation?
A
- Intramembranous
- Endochondral
4
Q
When does intramembranous ossification begin?
A
In the embryo at week 8
5
Q
Mesenchymal cells condense and differentiate into _____ via the transcription factor _____
A
osteoblasts; CBFA1 (core binding factor alpha)
6
Q
True/False: Bone forms via a cartilage model
A
FALSE!!! Bone forms directly from mesenchyme NOT via a cartilage model
7
Q
What do osteoblast secrete? What does it do?
A
osteoid (bone matrix); calcifies
8
Q
Osteoblasts within the matrix become which type of cell following mineralization?
A
osteocytes
9
Q
What type of bone, also called primary bone, forms with incoming blood vessels?
A
Woven bone
10
Q
Vascularized mesenchyme condenses on the external face of the woven bone to become what?
A
periosteum
11
Q
What type of bone replaces woven bone?
A
Lamellar bone (secondary bone)
12
Q
What makes up lamellar bone?
A
Compact and spongy bone
13
Q
What are some specific bones that are formed from lamellar bone?
A
- Flat bones of the skull (cranial vault)
- Facial bones (zygomatic, maxilla, and mandible)
- Central part of the clavicle (collarbone)
14
Q
____________ just deep to the periosteum thicken, forming a woven bone collar that is later replaced with what type of bone?
A
Traceculae; mature lamellar bone
15
Q
Spongy bone (diploe), consisting of distinct trabeculae, persists internally and its vascular tissue becomes what?
A
Red marrow
16
Q
What is the first step in endochondral ossification?
A
Fetal hyaline cartilage model develops.
17
Q
In formation of the cartilage model, mesenchymal cells condense and form what?
A
The perichondrium, a CT layer
18
Q
During the first stage of endochondral ossification, perichondrial cells differentiate into which type of cells and what do they produce?
A
chondroblasts; cartilage matrix
19
Q
Which two things stimulate perichondrial cells to differentiate into chondroblasts?
A
- Fibroblast growth factor (FGF)
- Bone morphogenic protein (BMP)
20
Q
The cartilage model develops by which two processes?
A
Interstitial growth and appositional growth
21
Q
The cartilage model develops by interstitial and appositional growth, chondroblasts become which type of cells?
A
Chondrocytes
22
Q
What is the second stage of endochondral ossification?
A
Cartilage calcifies and bone collar forms around diaphysis (shaft)
23
Q
During the process of cartilage calcification, perichondrium is invaded by _________ and becomes __________.
A
Vessels; periosteum
24
During cartilage calcification, which cells in the periosteum lay down collar of bone around the diaphysis?
Osteoblasts
25
During cartilage calcification (stage 2), what happens to chondrocytes?
They hypertrophy and die.
26
During cartilage calcification, blood vessels grow toward __________, carrying which type of cells?
cartilage; osteoblasts (from oseoprogenitors)
27
What is the third step of endochondral ossification?
Primary ossification center forms in the diaphysis
28
Where does the primary ossification center form?
diaphysis
29
What is the fourth stage of endochondral ossification?
Secondary ossification centers form in the epiphysis
30
Where does secondary ossification centers form?
epiphyses
31
When does secondary ossification occur?
Just before birth (some form postnatally)
32
When do secondary ossification centers close?
During puberty (up to early 20's)
33
What is the fifth step in endochondral ossification?
Cartilage is replaced by bone
34
What is an exception of the fifth stage of endochondral ossification? (Where is cartilage NOT replace by bone?)
Articular cartilage and the epiphyseal plate
35
What is the sixth, and last factor of enchondral ossification?
Epiphyseal plate is site of bone elongation, but then ossifies.
36
What forms the epiphyseal line?
Ossification of the epiphyseal plate
37
When does ossification of epiphyseal plates take place?
Between 10-25
38
Which bones have epiphyseal plates that are the last to ossify?
Clavicle
39
Which two areas fuse together when the epiphyseal plate ossifies?
the diaphysis and the epiphysis
40
After ossification of the epiphyseal plate, bone lengthening ceases, so any further growth is _________ at the ____________.
appositional; periosteum
41
Epiphyseal plate is the site of bone enlargement, which undergoes expansion ___________.
interstitially
42
Degeneration, calcification, and replacement by bone occurs nearer to which area of bone?
ossification centers
43
Interstitial growth occurs as _____________ undergo rapid mitosis and move into what formation?
chondrocytes; stack up in columns (bone lengthens)
44
Once interstitial growth ceases, chondrocytes stop dividing, undergo ____________ and form ____________
hypertrophy; lacunae
45
Where are hydroxyapatites found?
In the matrix of the cartilage
46
How is cartilage calcified?
Hydroxyapatite, along with alkaline phosphate, form crystal mineralization from inside the matrix
47
How do cartilage cells die?
apoptosis
48
True/False: Capillaries vascularize the calcified cartilage.
True
49
These cells, from osteoprogenitor cells, do this, in the function of replacing cartilage.
osteoblasts; deposit bone matrix
50
Osteoblasts continue calcification by secreting what material?
alkaline phosphate
51
Bone stores Ca++ and PO4- by ____________ collagen fibers with _______________.
mineralizing; hydroxyapetite
52
Hydroxyapetite consists of which 7 compounds?
Ca10, (PO4)6, (OH)2
| Mg, Na, K, and carbonate
53
Ca++ and PO4- are at near saturation levels, but are kept in which state by which enzyme?
solubilized; NPP1 (pyrophosphohydrolase)
54
How does NPP1 (pyrophosphohyrolase) keep Ca++ and PO4- soluable?
Hydrolyzes ATP and combines PO4- groups into pyrophosphate, PPi.
55
Which cells release alkaline phosphatase (ALP or TNAP)?
Osteoblasts
56
Osteoblast release of alkaline phosphate breaks down PPi to ____ which permits what?
PO4-; binding with Ca++
57
In non-bone tissue, hydroxyapetite formation is inhibited by...
pyrophosphate
58
Deficit of pyrophosphate, or excess of Ca++ and PO4- can cause mineralization of what?
```
soft tissues (arteries & veins)
degenerating tissues (blood clots)
```
59
Osteoblasts secrete matrix vesicles that contain what two compounds?
Ca++ and alkaline phosphatase (TNAP)
60
Secretion of matrix vesicles, containing Ca++ and TNAP allow for what process?
Cleavage of PPi, which permits crystallization
61
Matrix vesicles rupture, permitting precipitation of Ca++ and phosphate in which areas?
along collagen fibers in localized areas of bone
62
Limb bones develop solely via ...
endochondral ossification
63
In limb bone development, mesenchymal cells in center of limb condense into _______ _______.
precartilaginous aggregates
64
What do cartilagenous cells (chondroblasts) secrete?
BMP (bone morphogenetic protein)
| Ihh (Indian hedgehog)
65
What does BMP (bone morphogenetic protein) facilitate?
growth
66
What does Ihh (Indian Hedgehog) induce?
Further secretion of BMP (positive feedback)
67
In endochondral ossification of vertebrae, scleretomal cells differentiate into which cell type?
chondroblasts
68
In endochondral ossification of vertebrae, chondrification around the neural tube forms _____ _____?
cartilage models
69
In endochondral ossification of vertebrae, cartilage is replaced with bone which leaves ______ ______ between ossification centers (fuse during puberty)
cartilage plates
70
Primary ossification centers form vertebral sections that fuse between what ages?
3-5 years
71
Secondary ossification centers form on vertebral periphery during which phase of life?
Puberty
72
Growth of the body, especially bone, depends on which growth hormones? Secreted from which area of the body?
GH & IGF-1; secreted from the anterior pituitary gland
73
In general, hormones are secreted from the pituitary gland by actions from which area?
hypthalamic neurons
74
Pituitary gland extends down from the _________ and consists of which two portions?
hypothalamus; anterior & posterior
75
Hypothalamic neuro-secretory cells emit what onto local capillaries?
releasing hormones (RH)
76
When releasing hormones reach the anterior pituitary, it stimulates which cells to release anterior pituitary hormones into general circulation?
local endocrine cells (somatotrophs)
77
Growth hormone is released into the body by...?
hypthalamic - pituitary - GH axis
78
Growth Hormone Releasing Hormone (GHRH) is transported from the ___________ via which veins into the anterior pituitary?
hypothalamus; portal veins
79
GHRH Somatostatin from which two parts of the hypothalamus have which effect on the release of GH from the pituitary?
periventricular & arcuate; INHIBITS
80
Alternation of GHRH and SS stimulates a pulsatile release of Growth Hormone (GH) into circulation in what frequency?
every 3-4 hours
81
GH is released from cells of which area? Where does it go?
anterior pituitary cells; goes into circulation and targets various organs and structures
82
Growth hormone (GH) stimulates formation and release of which factor and from which locations?
Insulin-like Growth Factor (IGF-1); from liver and other tissues
83
What does IGF-1 mediate?
Growth promoting action of GH
84
What is the negative feedback on GH release?
GH and IGF-1
85
What are the two main areas of action?
Growth and metabolism
86
GH stimulates what type of growth and development both directly and indirectly through IGF-1?
Postnatal somatic growth
87
True/False: GH generates IGF-1 in very specific areas of the body.
FALSE!! GH generates IGF-1 throughout the entire body
88
IGF-1 is secreted from the liver as ________ or is generated within local structures as an _______ or ________.
Endocrine; autocrine/paracrine
89
IGF-1, induced by GH, stimulates development of which two systems, and which two types of tissue?
Nervous and immune; cartilage and adipose tissue
90
IGF increases organ size and function by stimulating what two things? Which organs are the exception?
protein synthesis and cell proliferation; (exception: gonads and brain)
91
GH/IGF promotes linear growth in bone and cartilage by stimulating what two processes of chondrocytes in endochondral ossification?
differentiation and proliferation
92
In metabolism, GH helps maintain what two things in adults?
normal lean body mass and bone mass
93
Metabolism is regulated in the short term by ______, and _____ in the long term.
insulin; GH/IGF
94
In metabolism, GH acts directly on what three tissues to shift the body's energy source from glucose to lipids, maintaining an adequate blood glucose reserve for the brain?
adipose, muscle, and liver
95
In metabolism, GH enhances muscle mass by enhancing which two processes?
amino acid absorption and protein synthesis
96
In metabolism, GH reduces adiposity and releases fatty acids by enhancing what process?
the lipolytic activity of endocrines such as norepinephrine
97
In metabolism of adipose, obesity _______ basal and stimulated GH secretion.
decreases
98
In metabolism in the liver, GH stimulates the synthesis and release of _____ and decreases _________ ________.
IGF; carbohydrate (i.e. glycogen) utilization
99
What are factors that upregulate GH?
Fasting, stress, sympathetic system
100
What factors down regulate GH?
Malnutrition and illness
101
What factors suppress GH?
obesity, cortisol, and FFA
102
GH enhances bone growth by initiating cell division among which type of cells?
prechondrocytes
103
When enhancing cell growth, GH stimulates synthesis and release of IGF-1 in which type of cells as paracrines or autocrines?
progenitor cells
104
What factor increases further replication of chondroblasts causing the tissue to grow?
IGF-1
105
Other endocrines facilitate bone growth; what does vitamin A facilitate?
Osteoblast formation
106
Other endocrines facilitate bone growth; what does thyroid hormone enhance?
Chondrocyte proliferation and hypertrophy
107
Estrogen induces pubertal growth spurt by what process?
Stimulation of the GH-IGF axis
108
Later in puberty, estrogen accelerates what?
growth plate senescence
109
What happens during growth plate senescence?
It slows cartilage proliferation leading to early closure
110
Glucocorticoids (cortisol) slows longitudinal bone growth by inhibiting what 3 processes?
chondrocyte proliferation, hypertrophy, and cartilage matrix synthesis
111
What are disorders of GH secretion often related to?
Dysregulation in the pituitary
112
What issue is a result of a GH deficiency?
Dwarfism (some cases due to decreases in IGF)
113
What two conditions are a result of GH excess?
Gigantism (youth)
| Acromegaly (in adult)
114
Growth accelerated prior to epiphyseal closure is a result of what condition?
Gigantism
115
Increased bone thickness (esp. hands, feet, and membranous bones of head) is a result of what condition?
Acromegaly
116
Bone remodeling is due to differential deposition of bone by ________ and resorption of bone by __________
osteoblasts; osteoclasts
117
Osteoblasts are derived from which type of cell?
Osteoprogenitor cells
118
Osteoclasts are derived from what type of cells?
mononuclear hemopoietic progenitor cells
119
Osteoblasts activate osteoclast precursors with _______
RANKL
120
RANKL is a cytokine from which two types of cells?
Osteoblasts and marrow stromal cells
121
RANKL is inhibited by _____ from osteoblasts
OPG
122
What are the 3 cycles of bone remodeling?
- Initiation (bone resorption)
- Transition
- Bone Formation
123
How are monocytes recruited by osteoclast precursors?
Signals from osteocytes as a result of a reduction in mechanical loading or microdamage in bone
124
Once monocytes are recruited by the osteoclast precursors, they are differentiated into osteoclasts by ________ from osteocytes (from osteoblasts ONLY in development)
RANKL
125
After osteoclasts excavate a resorption cavity, how is resorption terminated?
Osteoclast apoptosis
126
During the transition cycle of bone remodeling, osteoprogenitor cells enter from ________ .
marrow
127
Entry of osteoprogenitor cells from the marrow is regulated by which factors? And they are liberated from which area?
```
IGF-1
TGF
FGF
BMP
All liberated from resorbed bone matrix
```
128
During bone formation osteoblasts deposit _____ for the process of _______
osteoid; mineralization
129
What are the 3 fates of osteoblasts during bone formation?
- apoptosis
- become bone lining cells
- become osteocytes within matrix
130
There is alternation between bone resorption and deposition. During this process osteoblasts and osteoclasts release signaling factors that have what effect on each other's actions during remodeling?
They inhibit each other's actions
131
True/False: Bone is remodeled by selective deposition and resorption of bone from opposing surfaces.
True
132
At the epiphyseal plates, diaphyseal bone is resorbed _________ and deposited _______ for what purpose?
internally; externally; to maintain shape of the bone
133
In the face, the maxilla grows by ____ _____ in the posterior as well as upward and downward directions
net growth
134
What is a common site of hip breakage in the elderly (osteoporosis)?
Compression and tension trabeculae in the femoral neck.
