Asperosaponin VI suppresses ferroptosis in chondrocytes and ameliorates osteoarthritis by modulating the Nrf2/GPX4/HO-1 signaling pathway
Zhimeng Zhang,
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Daotong Yuan,
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Ximin Jin
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et al.
Frontiers in Pharmacology,
Journal Year:
2025,
Volume and Issue:
16
Published: Feb. 28, 2025
Background
Asperosaponin
VI
(AVI)
is
a
naturally
occurring
monosaccharide
derived
from
Dipsacus
asperoides
renowned
for
its
anti-inflammatory
and
bone-protective
properties.
Objective
To
elucidate
the
specific
mechanism
through
which
AVI
affects
chondrocytes
in
osteoarthritis
(OA).
Methods
For
vitro
experiments,
primary
were
to
molecular
mechanisms
underlying
action
of
AVI.For
vivo
rat
OA
models
established
using
modified
Hulth
method.
The
severity
knee
was
evaluated
8
weeks
post-surgery.
Micro-CT
imaging,
hematoxylin-eosin
staining,
Safranin
O-fast
green
staining
used
assess
degeneration
joints.
Immunohistochemistry
techniques
conducted
measure
levels
collagen
II,
MMP13,
Nrf2,
GPX4,
ACSL4,
HO-1
within
cartilage
tissues.
ELISA
assays
performed
those
TNF-α,
IL
-6,
PGE2
serum
samples.
Results
alleviated
chondrocyte
apoptosis
extracellular
matrix
degradation
induced
by
IL-1β.
It
attenuated
IL-6,
while
reducing
Fe
2+
malondialdehyde
(MDA).
upregulated
expression
HO-1,
GPX4
downregulating
that
ACSL4.
Mechanistic
studies
revealed
ML385-induced
inhibition
Nrf2
signaling
pathway
reversed
increase
ACSL4
increased
MDA
levels;
treatment
with
erastin,
ferroptosis
inducer,
produced
comparable
results.
In
experiments
demonstrated
improved
bone
volume/tissue
volume
trabecular
separation
values
rats;
Osteoarthritis
Research
Society
International
score;
expression;
downregulated
MMP13
expression,
decreased
PGE2.
Conclusion
Our
findings
suggest
promising
therapeutic
agent
OA.
exerted
protective
effect
regulating
Nrf2/GPX4/HO-1
axis
inhibit
cell
improve
osteoarthritis.
Language: Английский
Positive regulation Asperosaponin VI accumulation by DaERF9 through JA signaling in Dipsacus asper
Huanhuan Yang,
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Jiao Xu,
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Chunyun Xu
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et al.
BMC Plant Biology,
Journal Year:
2025,
Volume and Issue:
25(1)
Published: May 9, 2025
Language: Английский
Ferroptosis in osteogenic differentiation: a narrative review of bone regeneration metabolism
Lei Huang,
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Jiayi Wang,
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Jin Xu
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et al.
Regenerative medicine reports .,
Journal Year:
2025,
Volume and Issue:
unknown
Published: May 12, 2025
Bone
healing
is
a
complex
multifactor
and
diverse
physiological
process.
In
terms
of
osteogenic
differentiation,
different
types
regulated
cell
death,
such
as
ferroptosis,
play
key
roles
in
the
bone
microenvironment.
Ferroptosis
new
type
death
discovered
2012.
It
characterized
by
lipid
peroxidation
iron-dependent
accumulation,
which
are
closely
related
to
various
clinical
challenges.
recent
years,
an
increasing
number
studies
have
indicated
strong
potential
relationship
between
ferroptosis
orthopedic
diseases,
including
osteoporosis,
osteopenia
osteoarthritis.
Hence,
in-depth
investigation
metabolism
highly
important
for
treatment
diseases.
Moreover,
also
accompanied
morphological
changes
mitochondria,
increased
membrane
density
shrunken
been
detected
osteoblasts,
marrow
stem
mesenchymal
cells
osteoclasts.
The
inhibition
can
reduce
mitochondrial
damage,
alleviate
oxidative
stress
promote
regeneration.
This
article
reviews
mechanism
from
aspects
iron
overload
regulation
ferroptosis-related
pathways,
well
their
effects
on
Increasing
evidence
has
shown
that
defect
regeneration
processes
abnormal
metabolism.
Inhibiting
BMSCs
or
OBs
effectively
improve
rate
progression.
We
discuss
detailed
summarize
current
research
disease
treatment.
Language: Английский