Research Square (Research Square),
Год журнала:
2023,
Номер
unknown
Опубликована: Ноя. 30, 2023
Abstract
Background:
Osteoking
has
been
used
for
fracture
therapy
with
a
satisfying
clinical
efficacy.
However,
its
therapeutic
properties
and
the
underlying
mechanisms
remain
elusive.
Method:
A
bone
defect
rat
model
was
established
to
evaluate
pharmacological
effects
of
by
dynamic
observation
X-ray,
micro-CT
histopathologic
examination.
Transcriptome
profiling
performed
identify
defect-related
genes
effective
targets.
Then,
"disease-related
gene-drug
target"
interaction
network
constructed
list
key
targets
were
screened,
which
experimentally
verified.
Results:
effectively
promoted
repair
in
rats
accelerating
cortical
growth
trabeculae.
Histopathologically,
displayed
lower
scores
bone,
cancellous
connection
than
normal
controls,
exerted
favorable
effect
dose-dependent
manner
(all
P<0.001).
The
abnormal
serum
levels
turnover
markers,
factors
metabolism-related
biochemical
indexes
also
reversed
treatment.
Following
transcriptome-based
investigation,
we
hypothesized
that
osteoking
might
attenuate
ZBP1-STAT1-PKR-MLKL-mediated
necroptosis
involved
into
defect.
Experimentally,
expression
ZBP1,
STAT1,
PKR
hallmark
inflammatory
cytokines
end
distinctly
elevated
rats,
but
all
treatment,
suppressed
activities
RIPK1,
RIPK3
MLKL
tissue
supernatants.
Conclusions:
may
promote
formation
regulating
ZBP1-STAT1-PKR
axis,
leading
inhibit
RIPK1/RIPK3/MLKL
activation-mediated
necroptosis.
Biomedicine & Pharmacotherapy,
Год журнала:
2023,
Номер
169, С. 115864 - 115864
Опубликована: Ноя. 9, 2023
Osteoporosis
(OP)
is
characterized
by
reduced
bone
mass,
decreased
strength,
and
enhanced
fragility
fracture
risk.
Activating
transcription
factor
4
(ATF4)
plays
a
role
in
cell
differentiation,
proliferation,
apoptosis,
redox
balance,
amino
acid
uptake,
glycolipid
metabolism.
ATF4
induces
the
differentiation
of
marrow
mesenchymal
stem
cells
(BM-MSCs)
into
osteoblasts,
increases
osteoblast
activity,
inhibits
osteoclast
formation,
promoting
formation
remodeling.
In
addition,
mediates
energy
metabolism
osteoblasts
promotes
angiogenesis.
also
involved
mediation
adipogenesis.
can
selectively
accumulate
osteoblasts.
directly
interact
with
RUNT-related
2
(RUNX2)
up-regulate
expression
osteocalcin
(OCN)
osterix
(Osx).
Several
upstream
factors,
such
as
Wnt/β-catenin
BMP2/Smad
signaling
pathways,
have
been
ATF4-mediated
differentiation.
osteoclastogenesis
mediating
receptor
activator
nuclear
κ-B
(NF-κB)
ligand
(RANKL)
signaling.
agents,
parathyroid
(PTH),
melatonin,
natural
compounds,
reported
to
regulate
mediate
this
review,
we
comprehensively
discuss
biological
activities
maintaining
homeostasis
inhibiting
OP
development.
has
become
therapeutic
target
for
treatment.
Abstract
Background
Osteoking
has
been
used
for
fracture
therapy
with
a
satisfying
clinical
efficacy.
However,
its
therapeutic
properties
and
the
underlying
mechanisms
remain
elusive.
Method
A
bone
defect
rat
model
was
established
to
evaluate
pharmacological
effects
of
by
dynamic
observation
X-ray,
micro-CT
histopathologic
examination.
Transcriptome
profiling
performed
identify
defect-related
genes
effective
targets.
Then,
“disease-related
gene–drug
target”
interaction
network
constructed
list
key
targets
were
screened,
which
experimentally
verified.
Results
effectively
promoted
repair
in
rats
accelerating
cortical
growth
trabeculae.
Histopathologically,
displayed
lower
scores
bone,
cancellous
connection
than
normal
controls.
In
contrast,
exerted
favorable
effect
dose-dependent
manner.
The
abnormal
serum
levels
turnover
markers,
factors
metabolism-related
biochemical
indexes
also
reversed
treatment.
Following
transcriptome-based
investigation,
we
hypothesized
that
osteoking
might
attenuate
ZBP1–STAT1–PKR–MLKL-mediated
necroptosis
involved
into
defect.
Experimentally,
expression
ZBP1,
STAT1,
PKR
hallmark
inflammatory
cytokines
end
distinctly
elevated
rats,
but
all
treatment,
suppressed
activities
RIPK1,
RIPK3
MLKL
tissue
supernatants.
Conclusions
may
promote
formation
regulating
ZBP1–STAT1–PKR
axis,
leading
inhibit
RIPK1/RIPK3/MLKL
activation-mediated
necroptosis.
Chemistry of Materials,
Год журнала:
2024,
Номер
36(7), С. 3381 - 3394
Опубликована: Март 20, 2024
Although
hydrogel-loaded
drugs
hold
potential
for
treating
osteoporotic
bone
defects,
there
is
no
example
that
meets
the
release
requirement
repair
of
>3
months
owing
to
difficulty
in
overcoming
diffusion
drug
release.
Herein,
a
degradation-dependent
self-release
(DDSR)
hydrogel
negated
was
developed
by
polymerizing
only
natural
antioxidant
lipoic
acid
(LA).
By
controlling
just
degradation
rate
hydrogel,
LA
sustained
from
poly(LA)
backbone
and
achieved
∼4
antioxidation
anti-inflammation.
After
12
weeks
implantation,
new
formation
ratio
defects
treated
using
DDSR
ran
46
±
5.7%,
considerably
higher
than
untreated
(25.4
4.2%)
even
approaching
normal
(48.7
7.1%).
Notably,
could
also
serve
as
carriers
load
osteoinductive
nanohydroxyapatite,
thus
further
accelerating
repair.
The
with
constitutes
first
>3-month
Cell Death and Differentiation,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 10, 2025
Abstract
During
the
early
stage
of
tissue
injury,
macrophages
play
important
roles
in
activation
stem
cells
for
further
regeneration.
However,
regulation
during
bone
regeneration
remains
unclear.
Here,
extracellular
matrix
(ECM)
tenascin-C
(TNC)
is
found
to
express
periosteum
and
recruit
inflammatory
macrophages.
TNC-deficiency
delays
repair.
Transplantation
derived
from
injured
able
rescue
decreased
skeletal
impaired
caused
by
TNC
deficiency.
The
cell
communication
analysis
identifies
ITGA7
as
a
receptor
contributing
recruitment
expression
declines
aged
mice
exogenous
delivery
significantly
promotes
after
aging
through
Taken
together,
this
study
reveals
macrophage
its
function
providing
strategy
accelerate
delivery.
Biology,
Год журнала:
2025,
Номер
14(2), С. 107 - 107
Опубликована: Янв. 21, 2025
Dental
socket
repair
theoretically
involves
a
constructive
inflammatory
immune
response,
which
evolves
from
an
initial
M1
prevalence
to
subsequent
M2
dominance.
In
this
scenario,
the
MEK1/2
signaling
pathway
is
allegedly
involved
in
polarization.
This
study
aimed
evaluate
impact
of
pharmacological
inhibition
local
host
response
and
outcome.
C57Bl/6-WT
8-week-old
male
mice
were
submitted
extraction
right
upper
incisor
treated
(or
not,
control
group)
with
inhibitor
PD0325901
(10
mg/kg/24
h/IP,
MEK1/2i
analyzed
at
0,
3,
7,
14
days
using
microcomputed
tomography,
histomorphometry,
birefringence,
immunohistochemistry,
PCR
array
analysis.
The
results
demonstrate
that
limits
development
over
time,
being
associated
lower
expression
M2,
MSCs,
bone
markers,
levels
growth
osteogenic
factors,
along
higher
iNOS,
IL-1b,
IL-6,
TNF-α,
as
well
chemokines,
indicating
predominantly
pro-inflammatory
environment.
modulation
impaired
formation
demonstrated
by
microtomographic
histomorphometric
data.
show
delays
after
tooth
extraction,
supporting
concept
macrophages
are
essential
elements
for
regulation
proper
repair.
Gels,
Год журнала:
2025,
Номер
11(3), С. 190 - 190
Опубликована: Март 8, 2025
In
recent
years,
hydrogels
have
emerged
as
promising
candidates
for
bone
defect
repair
due
to
their
excellent
biocompatibility,
high
porosity,
and
water-retentive
properties.
However,
conventional
face
significant
challenges
in
clinical
translation,
including
brittleness,
low
mechanical
strength,
poorly
controlled
drug
degradation
rates.
To
address
these
limitations,
a
multifunctional
polymer,
polydopamine
(PDA)
has
shown
great
potential
both
regeneration
delivery
systems.
Its
robust
adhesive
properties,
responsiveness
photothermal
stimulation
make
it
an
ideal
candidate
enhancing
hydrogel
performance.
Integrating
PDA
into
not
only
improves
properties
but
also
creates
environment
conducive
cell
adhesion,
proliferation,
differentiation,
thereby
promoting
repair.
Moreover,
facilitates
release,
offering
approach
optimizing
treatment
outcomes.
This
paper
first
explores
the
mechanisms
through
which
promotes
regeneration,
laying
foundation
its
translation.
Additionally,
discusses
application
of
PDA-based
nanocomposite
advanced
systems
repair,
providing
valuable
insights
research
