Stem Cell Research & Therapy,
Год журнала:
2025,
Номер
16(1)
Опубликована: Фев. 25, 2025
This
study
mainly
explores
the
possible
role
and
mechanism
of
pyruvate
dehydrogenase
kinase
4
(PDK4)
in
onset
development
Glucocorticoid-induced
osteoporosis
(GIOP),
seeks
potential
targets
for
treatment
GIOP.
Mesenchymal
stem
cells
(MSCs)
were
treated
with
osteogenic
induction
medium.
An
vitro
damage
model
was
established
by
exposing
MSCs
to
a
high
concentration
(10−
6
M)
dexamethasone
(DEX).
Osteogenic
markers
measured
real-time
quantitative
polymerase
chain
reaction,
western
blot,
alkaline
phosphatase
staining,
Alizarin
Red
S
staining.
Ferroptosis
assessed
through
reactive
oxygen
species
(ROS)
fluorescent
probe,
transmission
electron
microscopy,
measurement
malondialdehyde
(MDA).
The
investigated
using
RT-qPCR,
lysosomal
probes,
molecular
docking,
other
analytical
approaches.
PDK4
validated
GIOP
rat
model,
micro-computed
tomography
Masson's
trichrome
High
concentrations
DEX
inhibited
differentiation
C3H10T1/2
cells,
exhibited
opposite
effect.
partially
reversed
inhibitory
effect
both
vivo
vitro.
caused
mitochondrial
shrinkage
disappearance
cristae
as
well
an
increase
total
iron,
ROS,
MDA
contents,
level
ferroptosis
key
factors.
These
changes
weakened
PDK4.
inhibitor
ferrostatin-1
blocked
DEX,
while
inducer
RSL3
reversal
reduced
protein
PDK4,
which
Bafilomycin
A1.
docking
results
showed
that
can
directly
bind
enhance
ability
bone
mass
rats.
may
promote
degradation
via
lysosome
pathway,
weaken
increasing
ferroptosis.
become
target
improving
Molecular Metabolism,
Год журнала:
2022,
Номер
60, С. 101470 - 101470
Опубликована: Март 15, 2022
With
long-term
metabolic
malfunction,
diabetes
can
cause
serious
damage
to
whole-body
tissue
and
organs,
resulting
in
a
variety
of
complications.
Therefore,
it
is
particularly
important
further
explore
the
pathogenesis
complications
develop
drugs
for
prevention
treatment.
In
recent
years,
different
from
apoptosis
necrosis,
ferroptosis
has
been
recognized
as
new
regulatory
mode
cell
death
involves
regulation
nuclear
receptor
coactivator
4
(NCOA4)-mediated
ferritinophagy.
Evidence
shows
that
ferritinophagy
play
significant
role
occurrence
development
Pharmacological Research,
Год журнала:
2022,
Номер
187, С. 106635 - 106635
Опубликована: Дек. 26, 2022
Osteoporosis
is
a
common
metabolic
bone
disease
that
results
from
the
imbalance
of
homeostasis
within
bone.
Intra-bone
dependent
on
precise
dynamic
balance
between
resorption
by
osteoclasts
and
formation
mesenchymal
lineage
osteoblasts,
which
comprises
series
complex
highly
standardized
steps.
Programmed
cell
death
(PCD)
(e.g.,
apoptosis,
autophagy,
ferroptosis,
pyroptosis,
necroptosis)
process
involves
cascade
gene
expression
events
with
tight
structures.
These
play
certain
role
in
regulating
metabolism
determining
fate
cells.
Moreover,
existing
research
has
suggested
natural
products
derived
wide
variety
dietary
components
medicinal
plants
modulate
PCDs
based
different
mechanisms,
show
great
potential
for
prevention
treatment
osteoporosis,
thus
revealing
emergence
more
acceptable
complementary
alternative
drugs
lower
costs,
fewer
side
effects
long-term
application.
Accordingly,
this
review
summarizes
types
field
osteoporosis.
perspective
targeting
PCDs,
also
discussed
roles
currently
reported
osteoporosis
involved
mechanisms.
Based
this,
provides
insights
into
new
molecular
mechanisms
reference
developing
anti-osteoporosis
future.
Abstract
Ferroptosis,
a
unique
type
of
cell
death,
is
characterized
by
iron-dependent
accumulation
and
lipid
peroxidation.
It
closely
related
to
multiple
biological
processes,
including
iron
metabolism,
polyunsaturated
fatty
acid
the
biosynthesis
compounds
with
antioxidant
activities,
glutathione.
In
past
10
years,
increasing
evidence
has
indicated
potentially
strong
relationship
between
ferroptosis
onset
progression
age-related
orthopedic
diseases,
such
as
osteoporosis
osteoarthritis.
Therefore,
in-depth
knowledge
regulatory
mechanisms
in
diseases
may
help
improve
disease
treatment
prevention.
This
review
provides
an
overview
recent
research
on
its
influences
bone
cartilage
homeostasis.
begins
brief
systemic
metabolism
ferroptosis,
particularly
potential
ferroptosis.
presents
discussion
role
promotion
loss
degradation
inhibition
osteogenesis.
Finally,
it
focuses
future
targeting
treat
intention
inspiring
further
clinical
development
therapeutic
strategies.
Frontiers in Endocrinology,
Год журнала:
2022,
Номер
13
Опубликована: Март 29, 2022
The
global
diabetes
epidemic
and
its
complications
are
increasing,
thereby
posing
a
major
threat
to
public
health.
A
comprehensive
understanding
of
mellitus
(DM)
is
necessary
for
the
development
effective
treatments.
Ferroptosis
newly
identified
form
programmed
cell
death
caused
by
production
reactive
oxygen
species
an
imbalance
in
iron
homeostasis.
Increasing
evidence
suggests
that
ferroptosis
plays
pivotal
role
pathogenesis
diabetes-related
complications.
In
this
review,
we
summarize
potential
impact
regulatory
mechanisms
on
complications,
as
well
inhibitors
diabetic
Therefore,
developing
drugs
or
agents
target
may
provide
new
treatment
strategies
patients
with
diabetes.
International Journal of Biological Sciences,
Год журнала:
2022,
Номер
18(10), С. 4118 - 4134
Опубликована: Янв. 1, 2022
A
variety
of
programmed
cell
death
types
have
been
shown
to
participate
in
the
loss
smooth
muscle
cells
(SMCs)
during
development
aortic
dissection
(AD),
but
it
is
still
largely
unclear
whether
ferroptosis
involved
AD.In
present
study,
we
found
that
expression
key
regulatory
proteins,
solute
carrier
family
7
member
11
(SLC7A11),
suppressor
protein
1
(FSP1)
and
glutathione
peroxidase
4
(GPX4)
were
downregulated
aortas
Stanford
type
AD
(TAAD)
patients,
liproxstatin-1,
a
specific
inhibitor
ferroptosis,
obviously
abolished
β-aminopropionitrile
(BAPN)-induced
rupture
mice.Furthermore,
methyltransferase-like
3
(METTL3),
major
methyltransferase
RNA
m
6
A,
was
remarkably
upregulated
TAAD
levels
METTL3
negatively
correlated
with
SLC7A11
FSP1
human
aortas.Overexpression
SMCs
(HASMCs)
inhibited,
while
knockdown
promoted
expression.More
importantly,
overexpression
facilitated
imidazole
ketone
erastin-and
cystine
deprivation-induced
repressed
HASMCs.Overexpression
either
or
abrogated
effect
on
HASMC
ferroptosis.Therefore,
revealed
critical
cause
both
humans
mice
promotes
HASMCs
by
inhibiting
FSP1.Thus,
targeting
methylation
potential
novel
strategy
for
treatment
AD.
Journal of Agricultural and Food Chemistry,
Год журнала:
2023,
Номер
71(6), С. 2745 - 2761
Опубликована: Янв. 31, 2023
Type
2
diabetic
osteoporosis
(T2DOP)
is
a
chronic
bone
metabolic
disease.
Compared
with
traditional
menopausal
osteoporosis,
the
long-term
high
glucose
(HG)
microenvironment
increases
patients'
risk
of
fracture
and
osteonecrosis.
We
were
accumulating
evidence
that
implicated
ferroptosis
as
pivotal
mechanism
glucolipotoxicity-mediated
death
osteocytes
osteoblast,
novel
form
programmed
cell
resulting
from
uncontrolled
lipid
peroxidation
depending
on
iron.
Vitamin
K2
(VK2),
fat-soluble
vitamin,
clinically
applied
to
prevent
improve
coagulation.
This
study
aimed
clarify
role
VK2
in
HG-mediated
ferroptosis.
established
mouse
T2DOP
model
by
intraperitoneal
injection
streptozotocin
solution
high-fat
high-sugar
diet.
also
cultured
marrow
mesenchymal
stem
cells
(BMSCs)
HG
simulate
environment
vitro.
Based
our
data,
inhibited
loss
ferroptosis,
latter
manifested
decreased
levels
mitochondrial
reactive
oxygen
species,
peroxidation,
malondialdehyde
increased
glutathione
In
addition,
treatment
was
capable
restoring
mass
strengthening
expression
SIRT1,
GPX4,
osteogenic
markers
distal
femurs.
As
for
further
exploration,
we
found
could
activate
AMPK/SIRT1
signaling,
knockdown
SIRT1
siRNA
prevented
VK2-mediated
positive
effect
HG-cultured
BMSCs.
Summarily,
ameliorate
through
activation
signaling
pathway
inhibit
Biomedicine & Pharmacotherapy,
Год журнала:
2023,
Номер
168, С. 115802 - 115802
Опубликована: Окт. 31, 2023
Diabetes
mellitus
is
a
metabolic
disease
caused
by
disorders
of
insulin
secretion
and
utilization.
Long-term
hyperglycemia,
resistance,
glucose
lipid
metabolism
cause
vascular
endothelial
cell
damage.
Endothelial
dysfunction
key
feature
diabetic
complications
such
as
nephropathy,
retinopathy,
neuropathy,
atherosclerosis.
Importantly,
death
thought
to
be
factor
contributing
injury.
Morphologically,
can
divided
into
three
forms:
type
I
apoptosis,
II
autophagy,
III
necrosis.
According
the
difference
in
function,
accidental
(ACD)
regulated
(RCD).
RCD
controlled
process
involving
numerous
proteins
precise
signaling
cascades.
Multiple
subroutines
covered
may
involved
dysfunction,
including
necroptosis,
pyroptosis,
entosis,
ferroptosis,
ferroautophagy,
parthanatos,
netotic
death,
lysosome-dependent
alkaliptosis,
oxeiptosis,
cuproptosis,
PANoptosis.
This
article
briefly
reviews
mechanism
significance
associated
with
which
will
help
deepen
understanding
provide
new
therapeutic
ideas.
Journal of Translational Medicine,
Год журнала:
2024,
Номер
22(1)
Опубликована: Апрель 30, 2024
With
the
aging
global
population,
type
2
diabetes
mellitus
(T2DM)
and
osteoporosis(OP)
are
becoming
increasingly
prevalent.
Diabetic
osteoporosis
(DOP)
is
a
metabolic
bone
disorder
characterized
by
abnormal
tissue
structure
reduced
strength
in
patients
with
diabetes.
Studies
have
revealed
close
association
among
diabetes,
increased
fracture
risk,
disturbances
iron
metabolism.
This
review
explores
concept
of
ferroptosis,
non-apoptotic
cell
death
process
dependent
on
intracellular
iron,
focusing
its
role
DOP.
Iron-dependent
lipid
peroxidation,
particularly
impacting
pancreatic
β-cells,
osteoblasts
(OBs)
osteoclasts
(OCs),
contributes
to
The
intricate
interplay
between
dysregulation,
which
comprises
deficiency
overload,
DOP
has
been
discussed,
emphasizing
how
excessive
accumulation
triggers
ferroptosis
concise
overview
highlights
need
understand
complex
relationship
T2DM
OP,
ferroptosis.
aimed
elucidate
pathogenesis
provide
prospective
for
future
research
targeting
interventions
field
