Journal of Inflammation Research,
Год журнала:
2023,
Номер
Volume 16, С. 4661 - 4677
Опубликована: Окт. 1, 2023
Abstract:
Ferroptosis
is
a
new
cell
fate
decision
discovered
in
recent
years.
Unlike
apoptosis,
autophagy
or
pyroptosis,
ferroptosis
characterized
by
iron-dependent
lipid
peroxidation
and
mitochondrial
morphological
changes.
involved
variety
of
physiological
pathological
processes.
Since
its
discovery,
has
been
increasingly
studied
concerning
bone-related
diseases.
In
this
review,
we
focus
on
the
latest
research
progress
prospects,
summarize
regulatory
mechanisms
ferroptosis,
discuss
role
pathogenesis
diseases,
such
as
osteoporosis
(OP),
osteoarthritis
(OA),
rheumatoid
arthritis
(RA),
osteosarcoma
(OS),
well
therapeutic
potential.
Keywords:
death,
iron
accumulation,
peroxidation,
diseases
Frontiers in Cell and Developmental Biology,
Год журнала:
2022,
Номер
9
Опубликована: Янв. 18, 2022
New
research
has
shown
that
the
development
of
osteoarthritis
(OA)
is
regulated
by
different
mechanisms
cell
death
and
types
cytokines.
Therefore,
elucidating
mechanism
action
among
various
cytokines,
processes
OA
important
towards
better
understanding
pathogenesis
progression
disease.
This
paper
reviews
in
relation
to
cytokine-triggered
death.
We
describe
morphological
features
molecular
pyroptosis,
apoptosis,
necroptosis,
ferroptosis,
summarize
current
findings
defining
between
OA.
Cell Proliferation,
Год журнала:
2021,
Номер
54(11)
Опубликована: Сен. 25, 2021
Abstract
Objectives
Chondrocyte
ferroptosis
contributes
to
osteoarthritis
(OA)
progression,
and
D‐mannose
shows
therapeutic
value
in
many
inflammatory
conditions.
Here,
we
investigated
whether
interferes
chondrocyte
ferroptotic
cell
death
during
osteoarthritic
cartilage
degeneration.
Materials
methods
In
vivo
anterior
cruciate
ligament
transection
(ACLT)‐induced
OA
mouse
model
an
vitro
study
of
chondrocytes
microenvironment
induced
by
interleukin‐1β
(IL‐1β)
exposure
were
employed.
Combined
with
Epas1
gene
gain‐
loss‐of‐function,
histology,
immunofluorescence,
quantitative
RT‐PCR,
Western
blot,
viability
flow
cytometry
experiments
performed
evaluate
the
chondroprotective
effects
progression
role
hypoxia‐inducible
factor
2
alpha
(HIF‐2
α)
D‐mannose‐induced
resistance
chondrocytes.
Results
exerted
a
effect
attenuating
sensitivity
alleviated
progression.
HIF‐2α
was
identified
as
central
mediator
Furthermore,
overexpression
Ad‐
intra‐articular
injection
abolished
eliminated
suppressor.
Conclusions
alleviates
suppressing
HIF‐2α‐mediated
ferroptosis,
indicating
be
potential
strategy
for
ferroptosis‐related
diseases.
Biomedicine & Pharmacotherapy,
Год журнала:
2022,
Номер
157, С. 113915 - 113915
Опубликована: Ноя. 12, 2022
Iron
homeostasis
plays
a
positive
role
in
articular
cartilage
health.
Excessive
iron
or
overload
can
induce
oxidative
stress
damage
chondrocytes
and
ferroptosis
cell
death,
advancing
knee
osteoarthritis
(KOA).
However,
up
to
date,
few
effective
agents
treat
overload-induced
KOA
(IOKOA).
Chinese
herbal
medicine
(CHM)
provides
abundant
resources
for
drug
selection
manage
bone
metabolic
conditions,
including
osteoporosis.
Biochanin
A
(BCA)
is
novel
bioactive
multifunctional
natural
compound
isolated
from
Huangqi,
which
has
protective
effects
on
loss.
Nevertheless,
the
function
mechanism
of
BCA
treating
IOKOA
are
still
elusive.This
study
seeks
uncover
potential
therapeutic
targets
mechanisms
management
with
accumulation.Iron
dextrin
(500
mg/kg)
was
intraperitoneally
injected
into
mice
establish
overloaded
model.
OA
induced
through
surgery,
progression
evaluated
eight
weeks
following
surgery.
severity
micro-CT
Safranin-O/Fast
green
staining
vivo.
deposition
joint
synovium
assessed
using
Perl's
Prussian
blue
staining.
Ferric
ammonium
citrate
(FAC)
then
administered
primary
evaluate
regulators
mediated
homeostasis.
Toluidine
utilized
identify
vitro.
The
vitality
cells
CCK-8
test.
apoptosis
rate
measured
Annexin
V-FITC/PI
assay.
intracellular
level
detected
utilizing
calcein-AM
Reactive
oxygen
species
(ROS),
lipid-ROS,
mitochondrial
membrane
potentiality
were
reflected
via
fluorescence
density.
Utilizing
RT-qPCR
western
blotting,
expression
determined.Micro-CT
histological
joints
showed
greater
degradation
higher
buildup
iron-overloaded
mice.
reduce
KOA.
assay
indicated
that
could
rescue
killed
by
iron.
Cell
rates
increased
due
but
improved
BCA.
Further,
content
iron,
ROS,
lipid-ROS
ferric
treatment
restored
after
different
concentrations
JC-1
revealed
overload.Iron
shown
promote
chondrocyte
vivo
Moreover,
suppressed
collagen
II
MMP
catalyzing
ROS
generation
dysfunction.
Our
results
directly
concentration
inhibiting
TfR1
promoting
FPN
also
target
Nrf2/system
xc-/GPX4
signaling
pathway
scavenge
free
radicals
prevent
lipid
peroxidation.
this
research
indicate
regulates
during
osteoarthritis,
open
new
field
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.
Signal Transduction and Targeted Therapy,
Год журнала:
2024,
Номер
9(1)
Опубликована: Окт. 14, 2024
Iron,
an
essential
mineral
in
the
body,
is
involved
numerous
physiological
processes,
making
maintenance
of
iron
homeostasis
crucial
for
overall
health.
Both
overload
and
deficiency
can
cause
various
disorders
human
diseases.
Ferroptosis,
a
form
cell
death
dependent
on
iron,
characterized
by
extensive
peroxidation
lipids.
Unlike
other
kinds
classical
unprogrammed
death,
ferroptosis
primarily
linked
to
disruptions
metabolism,
lipid
peroxidation,
antioxidant
system
imbalance.
Ferroptosis
regulated
through
transcription,
translation,
post-translational
modifications,
which
affect
cellular
sensitivity
ferroptosis.
Over
past
decade
or
so,
diseases
have
been
as
part
their
etiology,
including
cancers,
metabolic
disorders,
autoimmune
diseases,
central
nervous
cardiovascular
musculoskeletal
Ferroptosis-related
proteins
become
attractive
targets
many
major
that
are
currently
incurable,
some
regulators
shown
therapeutic
effects
clinical
trials
although
further
validation
potential
needed.
Therefore,
in-depth
analysis
its
molecular
mechanisms
may
offer
additional
strategies
prevention
treatment.
In
this
review,
we
discuss
significance
contribution
etiology
development
along
with
evidence
supporting
targeting
approach.
Importantly,
evaluate
recent
promising
interventions,
providing
guidance
future
targeted
treatment
therapies
against
Cell Death Discovery,
Год журнала:
2023,
Номер
9(1)
Опубликована: Авг. 29, 2023
Abstract
Osteoarthritis
(OA)
is
a
multifactorial
and
increasingly
prevalent
degenerative
disease
that
affects
the
whole
joint.
The
pathogenesis
of
OA
poorly
understood
there
lack
therapeutic
interventions
to
reverse
pathological
process
this
disease.
Accumulating
studies
have
shown
overproduction
reactive
oxygen
species
(ROS)
ROS-induced
lipid
peroxidation
are
involved
in
OA.
4-Hydroxy-2-nonenal
(4-HNE)
malondialdehyde
(MDA)
received
considerable
attention
for
their
role
cartilage
degeneration
subchondral
bone
remodeling
during
development.
Ferroptosis
form
cell
death
characterized
by
control
membrane
recent
suggested
chondrocyte
ferroptosis
contributes
progression.
In
review,
we
aim
discuss
peroxidation-derived
4-HNE
MDA
progression
addition,
potential
controlling
accumulation
inhibiting
discussed.
Abstract
Ferroptosis
is
an
iron‐dependent
cell
death
that
has
been
found
to
aggravate
the
progression
of
osteoarthritis
(OA)
and
gut
microbiota‐
OA
axis
refers
bidirectional
information
network
between
microbiota
OA,
which
may
provide
a
new
way
protect
OA.
However,
role
microbiota‐derived
metabolites
in
ferroptosis‐relative
remains
unclear.
The
objective
this
study
was
analyze
protective
effect
its
metabolite
capsiate
(CAT)
on
vivo
vitro
experiments.
From
June
2021
February
2022,
78
patients
were
evaluated
retrospectively
divided
into
two
groups:
health
group
(
n
=
39)
40).
Iron
oxidative
stress
indicators
determined
peripheral
blood
samples.
And
then
experiments,
surgically
destabilized
medial
meniscus
(DMM)
mice
model
established
treated
with
CAT
or
Ferric
Inhibitor‐1
(Fer‐1).
Solute
Carrier
Family
2
Member
1
(SLC2A1)
short
hairpin
RNA
(shRNA)
utilized
inhibit
SLC2A1
expression.
Serum
iron
increased
significantly
but
total
binding
capacity
decreased
than
healthy
people
p
<
0.0001).
least
absolute
shrinkage
selection
operator
clinical
prediction
suggested
serum
iron,
capacity,
transferrin,
superoxide
dismutase
all
independent
predictors
0.001).
Bioinformatics
results
SLC2A1,
Metastasis‐Associated
Lung
Adenocarcinoma
Transcript
(MALAT1),
HIF‐1α
(Hypoxia
Inducible
Factor
Alpha)‐related
signaling
pathways
play
important
homeostasis
In
addition,
16s
sequencing
untargeted
metabolomics
used
find
negatively
correlated
Osteoarthritis
Research
Society
International
(OARSI)
scores
for
chondrogenic
degeneration
0.0017).
Moreover,
reduced
ferroptosis‐dependent
vitro.
against
could
be
eliminated
by
silencing
SLC2A1.
upregulated
levels
DMM
group.
HIF‐1α,
MALAT1,
apoptosis
after
knockout
chondrocyte
cells
Finally,
downregulation
expression
Adeno‐associated
Virus
(AAV)
‐SLC2A1
shRNA
improves
vivo.
Our
findings
indicated
inhibited
HIF‐1a
activating