2/27 Reading Flashcards
1
Q
Fxn of osteocytes:
A
mechanosensors, control remodelling
2
Q
remodelling is controlled by:
A
local factors: growth factors, cytokines, systemic: calcitonin, strogen
3
Q
These are coupled:
A
bone resorption and formation
4
Q
Osteocyte apoptosis is followed by:
A
bone resorption (clasts)
5
Q
TF? Bone cells can communicate w other organs.
A
T. and vice versa
6
Q
4 types of cells of mineralized CT of bone:
A
blasts, clasts, cytes, and bone lining cells,
7
Q
Fxns of bone:
A
locomotion, support, protection of soft tissue, ca and P storage, bone marrow storage, bone endocrine functions (able to effect other organs)
8
Q
Fxn of bone lining cells:
A
resorption-formation coupling (possibly)
9
Q
3 phases of remodeling:
A
resorption initiation, transition (reversal period) from resorption to formation, formation
10
Q
Components of the basic multicellular unit:
A
blasts, clasts, cytes, and bone lining cells,
11
Q
This structure is required for formation:
A
BMU
12
Q
TF? BMU is a permanent anatomical structure.
A
F. temp
13
Q
remodeling is needed for:
A
fracture healing, skeletal adaptation to mechanic use, calcium homeostsis
14
Q
Excessive clast fxn leads to:
A
osteoporosis
15
Q
Excessive blast fxn leads to:
A
osteopetrosis
16
Q
bone homeostasis depends on:
A
local/ systemic factors, hormones, cytokines, chemokines, and biochemical stimulation
17
Q
Shape of blasts:
A
cuboidal
18
Q
% of bone occupied by blasts:
A
4-6%
19
Q
Location of blasts:
A
bone surface
20
Q
Morphological characteristics of blasts:
A
lots of RER and prominent golgi, many secretory vesicles
21
Q
How are blasts polarized?
A
secrete osteoid toward bone matrix,
22
Q
Blasts are derived from:
A
mesenchymal stem cells
23
Q
What is req for mesenchymal stem cells to commit to differentiate to the osteoprogenitor lineage?
A
expression of sp genes, then timely programmed steps, synthesis of bone morphogenic protein (BMP) and members of the Wingless (Wnt) pwy
24
Q
Expression of these is crucial for osteoblast differentiation:
A
Runt-reltated TF2, Distal-less homeobox5(Dlx5), osterix (Osx), Runx2
25
A master gene of osteoblast differentiation
Runx2
26
Runx2-null mice:
no blasts
27
Runx2 upregulates these genes:
ColIAI, ALP, BSP, BGLAP, OCN
28
Proliferation phase begins when:
a pool of blast progenitors expressing Runx2 and ColIAI has been established
29
What type of activity do blast progenitors show in proliferative phase?
alkaline phosphatase activity
30
blast progenitors are considered:
preosteoblasts
31
Transition from preosteoblasts to blasts is characterized by:
inc expression of Psx, secretion of bone matrix proteins like osteocalcin (OCN), bone sialoprotein (BSP) I/II and Type I collagen, cells become large, cuboidal
32
Other factors involved in blast differentiation:
FGF, microRNAs, connexon 43
33
FGF2-knockout mice:
dec bone mass coupled to inc of adipocytes in BM, indicating role in blast differentiation
34
Mechanism by which FGF-18 upregulates blast differentiation:
autocrine mechanism
35
Fxn of microRNAs:
regulate gene expression, some inc, some dec blast differentiation
36
The main connexin in bone:
Connexin 43
37
Mutation of gene encoding Connexin 43:
impaired blast differentiation, skeletal malformation
38
2 main steps to bone matrix synthesis:
deposition of organic matrix, mineralization
39
1st step of bone matrix synthesis:
blasts secrete collagen proteins, mainly type 1 collagen, non collagen proteins (OCN, osteonectin, BCP II, osteopontin) and proteoglycans including decorin and biglycan (all make organic matrix)
40
2 phases, organic matrix mineralization:
vesicular phase, fibrillar phase
41
When does vesicular phase occur:
portions of matrix vesicles released from apical membrane domain of blasts into new bone matrix
42
matrix vesicles released from apical membrane domain of blasts binds:
proteoglycans and other organic componenets
43
Charge of sulfated proteoglycans:
negative
44
Fxn of binding of matrix vesicles to sulfated proteoglycans:
immobilization of ca stored in matrix vesicles
45
When is ca released from proteoglycans and cross channels in matrix vesicle membrane?
When blasts secrete enzymes that degrade the proteoglycans
46
Ca channels in the matrix vesicle membrane are made by:
annexins
47
Compounds that are degraded by the ALP, secreted by osteoblasts:
phosphates
48
Cell that secretes ALP:
blasts
49
These are both required for HA formation :
ALP to release P, release of enzymes that degrade proteins from blasts (Ca release)
50
Where is HA formed?
In matrix vesicle
51
When does fibrillar phase occur:
when supersaturation of Ca and P inside the matrix vesicles leads to rupture, HA spreads to surrounding matrix
52
How many layers is the blast front?
1 layer
53
TF? Blasts have cytoplasmic process.
T. some, reach toward bone matrix and cyte processes
54
What happens to mature blasts in the fibrillar phase?
either undergo apoptosis or bc osteocyte or bone lining cell
55
These can be found inside the blast vacuoles:
round/ ovoid structures containing dense bodies --> blasts can phagocytose, engulf, and degrade apoptotic bodies during alveolar bone formation
56
Quiescent cells of the bone:
bone lining cells
57
Shape of bone lining cells:
flat shaped osteoblasts
58
Location of bone lining cells:
bone surfaces where neither resorption or formation is occurring
59
TF? Bone lining cells contain the same amt of rough RER and Golgi as blasts.
F. fewer
60
Processes of bone lining cells can extend to here:
into canaliculi
61
What hold bone lining cells and osteocytes together?
Gap junctions
62
What does the secretory activity of bone lining cells depend upon?
bone physiological status, can regain blast morphology and start secreting
63
Fxn, bone lining cells:
prevent direct interaction bw blasts and bone matrix, when bone resorption should not occur, participate in clast differentiation, producing osteoprotegerin (OPG) and the receptor activator of nuclear factor kappa-B ligand (RANKL)
64
% of total bone cells occupied by cytes:
90-95%
65
Life span of cytes:
up to 25y
66
Location of cytes:
within lacunae surrounded by mineralized bone matrix
67
Morphology of cytes:
dendritic
68
How does the morphology of cytes differ?
with the different types of bone
69
Osteocytes of trabecular bone:
more rounded than cytes of cortical bone (elongated)
70
Cytes are derived from:
MSC's, through blast differentiation
71
Are cytes formed through blast or clast differentiation?
blast
72
4 stages of cyte differentiation:
osteoid--cyte, preosteocyte, young -cyte, and mature -cyte
73
What happens at the end of a formation cycle?
subpop of blasts bc cytes incorporated into bone matrix, morphological change, ultrastructural change, reduction in blast size, organelles dec, N/C ratio inc, dec in protein synthesis and secretion
74
Effect of dec protein synthesis and secretion on the N/C ratio:
increases
75
protein E1/gp38 is aka:
podoplanin
76
Fxn of protein E1/gp38 (podoplanin):
cyte cytoplasmic process development, highly expressed in embedding or recently embedded cytes
77
Cells w dendritic morphology:
cytes, podocytes, Type II alveolar lung cells, cells of choroid plexus
78
How might E11/gp38 regulate actin cytoskeleton dynamics?
use GTPase activity to interact w cytoskeletal components and molecules involved in cell motility
79
Inhibition of E11/gp38 expression in cytes-like MLO-Y4 cells:
block dendritic elongation (podoplanin might be involved in dendrite formation in cytes)
80
Mature cyte stage:
totally entrapped in mineralized bone matrix
81
These are downregulated once the mature cyte stage has been reached:
OCN, BDPII, collagen Type I, ALP
82
These are highly expressed once the mature cyte stage has been reached:
osteocyte markers: dentine matrix protein 1 (DMP1), sclerostin
83
Location of cyte cell body:
lacuna
84
Location of cytoplasmic processes of cytes
cross tiny tunnels, canaliculi, forming the osteocyte lacunocanalicular system
85
How are the cytoplasmic process of cytes connected to each other?
gap junctions
86
Cytoplasmic processes of cytes connect to what other cell types?
cytes, blasts, bone lining cells
87
Fxn of lacunocanalicular system:
intercellular transport of small signalling molecules: prostaglandins, NO, oxygen and nutrient delivery to osteocytes due to close proximity of processes to vasculature
88
How does the sa of the osteocyte compare to that of the Haversian and Volkmann system?
osteocyte surface 400X larger
89
How many times larger is the osteocyte sa than the trabecular bone surface?
100X
90
Besides Gap junctions, how is cell-cell communication achieved?
by interstitial fluid bw cyte processes and canaliculi
91
This allows for cytes to acts as mechanosensors:
lacunocanalicular system
92
lacunocanalicular system can sense:
mechanical pressure and loads
93
Fxn of mechanosensor ability of lacunocanalicular system
bone adaptation to daily forces
94
How do cytes seem to be the orchestrators of remodeling?
Via the lacunocanalicular system, mechanosensor function
95
This is a chemotactic signal to clastic resorption:
cyte apoptosis
96
What happens to apoptotic cytes during resorption?
engulfed by clasts
97
How is the mechanosensory function of the lacunocanalicular system achieved?
strategic location of cytes in bone matrix, shape and spatial arrangement in agreement w their sensing and signalling transport functions
98
Define piezoelectric effect:
mechanical into biochemical signals (mechanosensory fxn of lacunocanalicular system)
99
2 proposed mechs for the piezoelectric effect:
1. protein complex formed by cilium and its assoc proteins PolyCysitns 1 and 2, crucial for cyte mechanosensing and blast/cytes-mediated formation 2. cyte cytoskeleton components (focal adhesion protein complex and its multiple actin-assoc proteins such as paxillin, vinculin, talin, and zyxin) stimulation --> cytes make several 2' msgs (ATP, NO, Ca, prostaglandins (PGE2, PGI2) --> influence bone physiology
100
Mechanosensory function would not be possible wo:
canalicular network
101
Terminally differentiated multinucleated cells:
clasts
102
Clasts originate from:
mononuclear cells, hematopoietic stem cell line
103
Factors that lead to the differentiation of hematopoietic stem cells to clasts:
mac-CSF, RANK ligand
104
M-CSF is secreted by:
osteoprogenitor mesenchymal cells and blasts
105
RANK ligand is secreted by:
blasts, cytes, and stromal cells
106
mac-CSF and RANK ligand together lead to:
activation of TF and gene expression in clasts
107
M-CSF receptor:
cFMS
108
Where is the M-CSF ligand located?
in clast precursors
109
Fxn of M-CSF binding cFMS:
inc proliferation of clast precursors, inhibit clast precursor apoptosis
110
This is crucial for osteoclastogenesis:
RANKL
111
Cell that expresses RANKL:
balsts, stromal cells, cytes
112
Where is the receptor for RANK?
clast precursors
113
Function of RANKL and RANK binding:
induction of clast formation
114
Cells that produce osteoprotegrin (OPG):
blasts, stromal cells, gingival and periodontal fibroblasts
115
OPG binds:
RANKL
116
Function of OPG binding RANKL:
inhibition of osteoclastogenesis due to blocking RANK/ RANKL interaction
117
RANK/ RANKL/ OPG system is a key mediator of:
osteoclastogenesis
118
RANK/ RANKL interactions promotes the expression of these osteogenic factors:
NFATc1, DC-STAMP
119
Fxn of NFATc1:
regulate clast specific genes that are crucial for clast activity by interacting w TFs, induces expression of Dc-STAMP
120
TF"s w which NFATc1 interacts to regulate clast activity:
PU.1, cFos, MITF
121
Osteoclast specific genes regulated by interaction of NFATc1 w TFs:
TRAP, cathepsin K
122
How does NFATc1 induce expression of Dc-STAMP?
under the influence of the RANKL/RANK interaction
123
What is Dc-STAMP needed for?
fusion of clast precursors
124
How might osteoclastogenic potential differ?
depending on bone site
125
TF? Clasts from long bone marrow are formed slower than in jaw.
F. faster
126
This may be responsible for the different dynamic of osteoclastogenic potential:
cellular composition of the bone-site specific marrow
127
When do clasts polarize?
during remodeling
128
How many clast membrane domains are visible during remodeling?
4: sealing zone, ruffled border, basolateral and functional secretory domains
129
Clast membrane domains in contact with the bone matrix:
sealing zone, ruffled border
130
Clast membrane domains not in contact with the bone matrix:
basolateral and functional secretory domains
131
What does polarization of clasts during resorption involve?
rearrangement of the actin cytoskeleton
132
What is formed in the cytoskeleton of clasts during remodeling for resorption?
F-actin ring, isolation of portion of membrane that develop into the ruffled border
133
What is the F-actin ring?
dense continuous zone of highly dynamic podosomes
134
When are the clast membrane domains formed?
only when clasts are in contact w extracellular mineralized matrix
135
Fxn of avB3-integrin and CD44:
attachment of clast podosomes to bone
136
This is a membrane domain formed by microvilli, isolated by surrounding clear zone
ruffled border
137
Cleas zone is aka:
sealing zone
138
What is the clear zone devoid of?
organelles
139
Location of clear zone:
periphery of the clast, adjacent to bone matrix
140
Forms the sealing zone:
actin ring, actin, talin, vinculin, paxillin, tensin, actin-asoc proteins such as a-actinin, fimbrin, gelsolin, dynamin
141
AvB3 binds:
noncollagenous bone matrix containing-RGD sequence such as bone sialoprotein, osteopontin, and vitronectin, establishing a peripheric sealing that delimits the central region, here the ruffled border is located
142
Location of ruffled border:
center
143
Maintenance of this is essential for clast activity:
ruffled border
144
Ruffled border is formed due to:
intense trafficking of lysosomal and endosomal components
145
This help to acidify the resorption lacuna, enabling dissolution of HA crystals
vacuole-type H+-ATpase in teh ruffled border
146
vacuole-type H+-ATpase is aka:
V-ATPase
147
Transportation of THESE within the ruffled border to HERE lead to bone degradation:
protons and enzymes: tartrate-resistnat acid phosphatase (TRAP), cathepsin K, matrix metalloproteinase-9 (MMP-9) transported to Howship lacuna
148
What happens to the degradation of bone in Howship's lacuna?
endocytosed across ruffled border and transcytosed to functional secretory domain at plasma membrane
149
This leads to osteoporosis:
Abnormal inc in clast formation and activity:
150
Abnormal inc in clast activity can also lead to:
bone metastases (results in periarticular erosions) and inflammatory arthritis (results in painful lesions)
151
Inflammatory cells in periodontitis produce:
chemical mediators: IL-6, RANKL
152
IL-6 and RANKL stimulate:
migration of clasts --> abnormal inc in bone resorption --> progression of periodontitis
153
Genetic mutation affecting formation and resorption functions of clasts:
osteopetrosis, dec bone resorption
154
Clasts produce THIS that controls blasts during remodeling:
clastokines (factors), involved in both resorption and cytokine secretion that influences the activity of other cells
155
Cell type that may directly regulate the hematopoietic stem cell niche:
clasts
156
Components of extracellular bone matrix:
inorganic salts, organic matrix
157
% of organic matrix taken up by collagenous proteins:
90%
158
Predominant collagen type of extracellular bone matrix:
Tyoe 1
159
These make up the organic portion of the extracellular bone matrix:
Type 1 collagen, non-collagenous proteins (osteocalcin, osteonectin, osteopontin fibronectin, bone sialoproteins (BPM), GF"s, small leucine-rich glycoproteins
160
small leucine-rich glycoproteins found in extracellular bone matrix:
decorin, biglycan, lumican, osteoderin, seric proteins
161
Inorganic portion of bone:
Ca, P, bicarbonate, sodium, potassium, sitrate, magnesium, carbonate, flourite, zinc, barium, strontium
162
HA chemical formula:
Ca10(PO4)6(OH)2
163
These form a scaffold for HA deposition:
collagen + noncollagenous matrix poteins
164
What is responsible for the stiffness and resistance of bone?
HA deposition into scaffold of collagenous and noncollagenous proteins
165
Functions of bone matrix:
mechanical support, bone homeostasis via release of several molecules that interfere in bone cell activity
166
These are believed to be important in understanding and prediction of bone fracture when loss of bone mass alone is insufficient to cause fracture
factors, including changes in bone matrix proteins and their modifications
167
Fxn of collagen:
structure and function of bone tissue
168
Factors that can lead to variation in concentration of bone matrix proteins:
age, nutrition, disease, antiosteoporotic tx
169
These can lead to postyield deformation and bone fracture:
age, nutrition, disease, antiosteoporotic tx
170
There is a possible relationship bw hyaluronic acid synthesis and:
inc in clast activity
171
What is the inc in hyaluronic acid synthesis after PTH tx related to:
subsequent bone resorption
172
Most common molecule involved in interactions bw bone cells and bone matrix:
integrins
173
Fxns of bone matrix:
support for bone cells, regulation of activity of bone cells through several adhesion molecules
174
How do blasts interact w bone matrix?
via integrins
175
integrins of blasts attach to:
RGD and other sequences in bone matrix proteins (osteopontin, fibronectin, collagen, osteopontin, bone sialoprotein
176
Most common integrins in blast:
a1B1, a2B1, and a5B1
177
Functions of a1B1, a2B1, and a5B1
cell-cell adhesion, blast organization on bone surface during osteoid synthesis
178
Why are interactions bw clasts and bone matrix essential for osteoid synthesis?
bone resorption only occurs when clasts bind to mineralized bone
179
What do clasts express during resorption?
avB3, a2B1 integrins to interact with extracellular matrix
180
These are required for clasts to interact with extracellular matrix:
avB3, a2B1 integrins
181
avB3 bind:
bone enriched, RGD-containing proteins such as bone sialoprotein and osteopontin
182
B1 integrins bind:
collagen fibrils
183
Do clasts express cadherins?
no, bc they are migrating cells
184
Where are cadherins found in bone?
contact bw clasts precursors and stromal cells
185
Stromal cells express:
GF for clast differentiation
186
Interaction integrins play a role in:
osteocyte-bone matrix interactions
187
osteocyte-bone matrix interactions are important for:
mechanosensitive function of cytes, whereby signals induced by tissue deformation are generated and amplified
188
Integrins suggested to be involved in cyte-bone matrix interaction:
B3, B1 (involved in mechanosensing)
189
B3 and B1 interaction occur bw:
cyte body and bone matrix of lacuna wall, bw cyte processes and canalicular wall
190
Fluid filled narrow space bw cyte body and processes from mineralized bone matrix:
pericellular space, non-organized pericellular matrix
191
Which is wider, space bw cyte cell body and lacunar wall or cyte processes and canalicular wall?
cell body and lacunar wall
192
Macromolecules present in pericellular fluid and produced by cytes::
osteopontin, osteocalcin, dentin matrix protein, proteoglycans, hyaluronic acid
193
Delicate fibrous connection in the canalicular network:
tethers, perlecan is a possible compound of tethers
194
Cytes can attach directly via:
hillocks, protruding structures from canalicular wall, form close contacts, possibly via B3-integrins, w the membrane of cyte processes, role in mechanosensation?, sensing fluid movement in pericellular space
195
Essential for bidirectional solute transport in pericellular space:
fluid flux movements
196
Bidirection solute transport influences:
cyte signalling pwy, communication bw bone cells
197
Local factors controlling formation, proliferation, differentiation and activity of remodeling:
autocrine and paracrine molecules: GF's, cytokines, prostaglandins produced by bone cells, factors of bone matrix released during bone resorption
198
Systemic factors important for bone homeostasis:
PTH, calcitonin,1,25-dihydroxyvitamin D3 (calcitrol), glucocorticoids, androgens, estrogens
199
2 molecule that can bind PTH receptor:
PTH, PTHrP (can influence bone remodeling)
200
Main cause of bone loss and osteoporosis:
dec in estrogen at menopause
201
How does estrogen maintain bone homeostasis?
inhibit blast and cyte apoptosis, prevent excessive resorption, suppress clast formation/ activity, induce clast apoptosis
202
How does estrogen dec clast formation?
by inhibiting synthesis of osteoclastogenic cytokine RNKL by blasts and cytes, by red level of other osteoclastogenic cytokines
203
Estrogen stimulates blasts and cytes to produce:
osteoprotegrin (OPG)
204
What is OPG?
decoy receptor of RNK in clast, inhibits osteoclastogenesis
205
osteoclastogenic cytokines:
IL-1, 6, 11, TNF-a/ -B, M-CSF
206
How does estrogen act directly on bone cells?
estrogen receptors a and B
207
This is a direct target of estrogen:
clast
208
This participates in control of clast life span:
estrogen, via estrogen receptors
209
Where does remodelling take place?
in bone cavities needed to be remodeled
210
This forms before remodeling begins:
BMU
211
These form the cutting cone ahead during remodeling:
clasts
212
These form the closing cone from behind during remodeling:
blasts
213
The closing cone is assoc w:
BV's and peripheral innervation
214
Its' suggested that the BMU is covered by:
a canopy of cells (possibly bone lining cells)
215
These cells form the bone remodelling compartment:
bone lining cells
216
What is the BRC connected to:
bone lining cells on bone surface, in communication w cytes in bone matrix
217
Bone remodelling cycle phases:
initiation phase, reversal, bone formation
218
Initiation phase consists of:
bone resorption, transition (reversal phase) phase of bone
219
Completes the bone remodeling cycle:
coordinated action of tes and bone lining cells
220
How are hematopoietic cells recruited in the initiation phase?
osteogenic factors: RANKL and M-CSF, then differentiate to mature clasts
221
Process during remodeling w direct and indirect communications among bone cells:
coupling mechanism, includes coupling factors stored in bone matrix that would be released after clast resorption
222
These can act as coupling factors:
insulin-like GF(IGF), TGF-B, BMP's, FGF, platelet-derived GF
223
Where are the coupling factors stored?
in bone matrix
224
When are coupling factors released?
during resorption
225
Category of molecule suggested to be involved in bone cell communication during remodeling:
semaphorins
226
this must be inhibited in the initiation phase of remodeling
blast activity and differentiation, to completely remove damaged or aged bone
227
Factor expressed by clasts that inhibits bone formation during resorption:
Sema4D
228
What are semaphorins:
large family of glycoproteins, membrane bound or soluble, in a wide range of tissues,
229
semaphorins are involved in:
immune response, organogenesis, CV development, tumor progression, cell-cell communication bw clasts and blasts during remodelling
230
Where is Sema4D expressed?
clasts
231
Receptor to Sema4D:
Plexin-B1
232
where is the Sema4D receptor located?
blasts
233
Fxn of binding Sema4D and Plexin-B1:
inhibits IGF-1 pwy
234
Fxn of IGF-1 pwy:
blast differentiation
235
How do clasts suppress bone formation?
by expressing Sema4D
236
member of Sema family found in blasts:
Sema3A
237
Fxn of Sema3A:
inhibitor of osteoclastogenesis
238
This is expressed by clasts to initiate bone resorption:
Sema4D
239
When is Sema3A expressed by blasts?
prior to bone formation
240
Fxn of ephrinB2:
bind ephrinB4, leading to transduction of bidirectional signals, promoting blast differentiation
241
Where is ephrinB2 expressed?
membrane of mature clasts, also in blasts
242
Where is ephrinB4 expressed?
membrane of blasts
243
***ephrinB4/ephrinB2 binding leads to:
inhibit formation of new clasts (this is the reversal signal)
244
***ephrinB2/ephrinB4 binding leads to:
promotes blast differentiation
245
Factors secreted by mature clasts that stimulate blast differentiation:
secreted signalling molecules Wnt10b, BMP6, and the signaling sphingolipid, sphingosine 1-phosphate
246
complex mech during remodeling
of ephrins w other factors in calst/blast communication
247
TF? direct communication bw mature blasts and clasts has been demonstrated.
F
248
How does mechanical loading effect cytes?
stimulate cytes to produce factors that exert anabolic action on bone
249
***These have anabolic actions on bone:
PGE, prostacyclin (PGI2), NO, and IGF-1
250
Effect of unloading on cytes:
Downregulates anabolic factors, stimulate cyte to produce sclerostin and DKK-1, specific factors that stimulate local osteoclastogenesis
251
***Fxn of sclerostin and DKK-1:
inhibit blast activity
252
Gene that makes sclerostin:
SOST gene
253
Fxn of sclerostin:
neg regulator of bone formation, by antagonizing in blasts the actions of Lrp5, a key receptor of the Wnt/B-catenin signalling pwy
254
What is Lrp5?
receptor of Wnt/B-catenin signalling pwy
255
chemotactic signal for local clast recruitment:
cyte apoptois
256
These engulf apoptotic cytes:
clasts
257
What can clasts remove from remodelling sites?
dying cytes and/or blasts
258
What produce osteoclastogenic factors nearby dying cytes?
viable cytes
259
Main source of RANKL to promote osteoclastogenesis:
cytes, also stromal cells, blasts, fibroblasts
260
What do viable osteocytes near apoptotic ones express?
high RANKL/ OPG ratio, inc level of VEGF, and monocyte chemoattractant protein-1 (CCL2) promoting inc in local osteoclastogenesis
261
What may induce the release of local proosteoclastogenic cytokines?
disruption in cell-cell communication bw osteocytes
262
These may be produced by osteocytes that stimulate osteoclast recruitment during remodeling:
high mobility group box protein 1 (HMGB1) and M-CSF
263
2 forms of osteocalcin:
carboxylated and undercarboxylated
264
**Which form of osteocalcin has high affinity to HA crystals:
carboxylated, it remains in bone matrix during mineralization
265
Why does the undercalcified show lower affinity to minerals:
due to acidification of bone matrix during resorption
266
To where is undercalcified osteocalcin shuttled:
other organs via blood stream
267
Where has undercalcified osteocalcin been shown to have effects?
pancreas, adipose tissue, nervous system
268
Effect of undercalcified osteocalcin in pancreas:
positive regulator of pancreatic insulin secretion/ sensitivity, proliferation of pancreatic B-cells
269
Fxn of undercalcified osteocalcin in adipoes tissue:
stimulates adiponectin gene expression --> enhances insulin sensitivity
270
Fxn of undercalcified osteocalcin in testis:
binds receptors in Leydig cells, enhances testosterone syntheses, increases fertility
271
Effects of undercalcified osteocalcin in brain:
stimulates synthesis of monoamine NTs' in hippocampus and inhibits gamma-aminobutyric acid (GABA) synthesis, improving memory and learning
272
Endocrine fxn of bone promoted by cytes:
regulate P metabolism via production of FGF23 --> acts on other organs inc parathyroid gland and kidneys to red circulating phosphates
273
***How do cytes act on immune system?
by modifying microenvironments in primary lymphoid organs, influencing lymphopoeisis
274
Cells that influence immune system, mainly upon bone inflammatory destruction:
cytes, blasts, and clasts
275
study of communication interplay bw skeletal and immune system:
osteoimmunology
276
This is responsible for bone formation and resorption:
bone matrix integrins-dependent bone cells interactions
