Frontiers in Immunology,
Год журнала:
2025,
Номер
16
Опубликована: Март 24, 2025
Background
Osteoarthritis
(OA)
is
a
chronic
joint
disease
that
significantly
impairs
quality
of
life.
Synovitis
plays
pivotal
role
in
OA
progression,
and
pyroptosis,
form
programmed
cell
death
associated
with
innate
immune
inflammation,
may
contribute
to
the
pathogenesis
synovitis.
Nevertheless,
precise
pyroptosis
remains
poorly
understood.
Methods
We
performed
an
analysis
bulk
RNA
sequencing
data
examine
expression
profiles
pyroptosis-related
genes
synovium.
A
LASSO-Cox
regression
model
was
employed
identify
genes.
Single-cell
were
used
validate
these
specific
synovial
clusters.
Differentially
expressed
(DEGs)
macrophages
high
or
low
levels
core
subjected
enrichment
analysis.
protein-protein
interaction
(PPI)
network
constructed
hub
genes,
potential
therapeutic
compounds
predicted.
Consensus
clustering
correlations
between
status.
After
identifying
PYCARD
as
gene
macrophages,
we
assessed
synovium
validated
its
related
M1
macrophages.
Results
total
twenty
DEGs
identified,
six
selected
through
LASSO
regression.
identified
key
Furthermore,
57
targeting
Validation
confirmed
upregulation
Conclusion
identified.
This
study
offers
valuable
insights
into
treatment
targets
for
OA.
International Journal of Molecular Sciences,
Год журнала:
2023,
Номер
24(7), С. 6405 - 6405
Опубликована: Март 29, 2023
Osteoarthritis
(OA)
is
a
chronic
disease
and
the
most
common
orthopedic
disorder.
A
vast
majority
of
social
OA
burden
related
to
hips
knees.
The
prevalence
knee
varied
across
studies
such
differences
are
reflected
by
heterogeneity
data
reported
conducted
worldwide.
complete
understanding
pathogenetic
mechanisms
underlying
this
pathology
essential.
inflammatory
process
starts
in
synovial
membrane
with
activation
immune
system,
involving
both
humoral
cellular
mediators.
crucial
role
played
so-called
“damage-associated
molecular
patterns”
(DAMPs).
Mesenchymal
stem
cells
(MSCs)
may
be
promising
option
among
all
possible
therapeutic
options.
However,
many
issues
still
debated,
as
best
cell
source,
their
nature,
right
amount.
Further
needed
clarify
remaining
doubts.
This
review
provides
an
overview
recent
relevant
on
mechanism
cartilage
damage
OA,
including
current
approaches
regenerative
medicine.
Journal of Nanobiotechnology,
Год журнала:
2024,
Номер
22(1)
Опубликована: Фев. 19, 2024
Osteoarthritis
(OA)
is
one
of
the
most
prevalent
chronic
musculoskeletal
diseases
among
elderly
population.
In
this
study,
macrophage-derived
exosomes
were
isolated
and
identified.
Exosomes
subjected
to
microRNA
(miRNA)
sequencing
bioinformatic
analysis,
differentially
expressed
miRNAs
verified.
miR-26b-5p
target
genes
confirmed
through
target-site
mutation
combined
with
a
dual-luciferase
reporter
assay.
The
effects
on
macrophage
polarization
chondrocyte
hypertrophy
assessed
in
vitro.
agomir
was
applied
mice
OA
induced
by
anterior
cruciate
ligament
transection
(ACLT).
therapeutic
evaluated
via
pain
behavior
experiments
histological
observations.
vitro,
repolarized
M1
macrophages
an
anti-inflammatory
M2
type
targeting
TLR3
signaling
pathway.
could
COL10A1,
further
inhibiting
macrophage-conditioned
medium
(M1-CM).
vivo,
ameliorated
gait
abnormalities
mechanical
allodynia
mice.
treatment
attenuated
synovitis
cartilage
degeneration,
thereby
delaying
progression.
conclusion,
exosomal
protect
articular
ameliorate
COL10A1.
affected
hypertrophy.
Thus,
miR-26b-5p-based
strategy
might
be
potential
method
for
treatment.
Advanced Materials,
Год журнала:
2024,
Номер
unknown
Опубликована: Апрель 29, 2024
Abstract
Intra‐articular
injection
of
drugs
is
an
effective
strategy
for
osteoarthritis
(OA)
treatment.
However,
the
complex
microenvironment
and
limited
joint
space
result
in
rapid
clearance
drugs.
Herein,
a
nanogel‐based
proposed
prolonged
drug
delivery
remodeling.
Nanogel
constructed
through
functionalization
hyaluronic
acid
(HA)
by
amide
reaction
on
surface
Kartogenin
(KGN)‐loaded
zeolitic
imidazolate
framework‐8
(denoted
as
KZIF@HA).
Leveraging
inherent
hydrophilicity
HA,
KZIF@HA
spontaneously
forms
nanogels,
ensuring
extended
release
OA
microenvironment.
exhibits
sustained
over
one
month,
with
low
leakage
risk
from
cavity
compared
to
KZIF,
enhanced
cartilage
penetration,
reparative
effects
chondrocytes.
Notably,
KGN
released
serves
promote
extracellular
matrix
(ECM)
secretion
hyaline
regeneration.
Zn
2+
reverses
progression
promoting
M2
macrophage
polarization
establish
anti‐inflammatory
Ultimately,
facilitates
regeneration
alleviation
within
three
months.
Transcriptome
sequencing
validates
that
stimulates
macrophages
secretes
IL‐10
inhibit
JNK
ERK
pathways,
chondrocytes
recovery
enhancing
ECM
This
pioneering
nanogel
system
offers
new
therapeutic
opportunities
release,
presenting
significant
stride
treatment
strategies.
Abstract
Osteoarthritis
(OA)
is
a
chronic
inflammatory
disease
characterized
by
cartilage
destruction,
synovitis,
and
osteophyte
formation.
Disease‐modifying
treatments
for
OA
are
currently
lacking.
Because
inflammation
mediated
an
imbalance
of
M1/M2
macrophages
in
the
synovial
cavities
contributes
to
progression,
regulating
M1
M2
polarization
can
be
potential
therapeutic
strategy.
Basing
on
inherent
immune
mechanism
pathological
environment
OA,
immunoglobulin
G‐conjugated
bilirubin/JPH203
self‐assembled
nanoparticle
(IgG/BRJ)
developed,
its
evaluated.
After
intra‐articular
administration,
IgG
conjugation
facilitates
recognition
engulfment
nanoparticles
macrophages.
The
internalized
disassemble
response
increased
oxidative
stress,
released
bilirubin
(BR)
JPH203
scavenge
reactive
oxygen
species
(ROS),
inhibit
nuclear
factor
kappa‐B
pathway,
suppress
activated
mammalian
target
rapamycin
result
repolarization
enhance
M2/M1
ratios.
Suppression
IgG/BRJ
promotes
protection
repair
rat
model,
thereby
improving
outcomes.
This
strategy
opsonization
involving
engulf
carrier‐free
BR/JPH203
therapy
holds
great
intervention
treatment.
Biomedicine & Pharmacotherapy,
Год журнала:
2024,
Номер
173, С. 116458 - 116458
Опубликована: Март 19, 2024
Osteoarthritis
(OA)
is
a
multifaceted
disease
characterized
by
imbalances
in
extracellular
matrix
metabolism,
chondrocyte
and
synoviocyte
senescence,
as
well
inflammatory
responses
mediated
macrophages.
Although
there
have
been
notable
advancements
pharmacological
surgical
interventions,
achieving
complete
remission
of
OA
remains
formidable
challenge,
oftentimes
accompanied
significant
side
effects.
Mesenchymal
stem
cells
(MSCs)
emerged
promising
avenue
for
treatment,
given
their
ability
to
differentiate
into
chondrocytes
facilitate
cartilage
repair,
thereby
mitigating
the
impact
an
microenvironment
induced
This
comprehensive
review
aims
provide
concise
overview
diverse
roles
played
MSCs
treatment
OA,
while
elucidating
underlying
mechanisms
behind
these
contributions.
Specifically,
include:
(a)
Promotion
regeneration;
(b)
Inhibition
degradation;
(c)
Attenuating
macrophage-induced
microenvironment;
(d)
Alleviation
pain.
Understanding
paramount
developing
novel
therapeutic
strategies.
By
harnessing
regenerative
potential
immunomodulatory
properties
MSCs,
it
may
be
possible
devise
more
effective
safer
approaches
managing
OA.
Further
research
clinical
studies
are
warranted
optimize
utilization
realize
full
field
therapeutics.
Frontiers in Immunology,
Год журнала:
2024,
Номер
14
Опубликована: Янв. 9, 2024
Osteoarthritis
(OA)
has
been
a
leading
cause
of
disability
in
the
elderly
and
there
remains
lack
effective
therapeutic
approaches
as
mechanisms
pathogenesis
progression
have
yet
to
be
elucidated.
As
OA
progresses,
cellular
metabolic
profiles
energy
production
are
altered,
emerging
reprogramming
highlights
importance
specific
pathways
disease
progression.
crucial
part
glucose
metabolism,
glycolysis
bridges
inflammatory
dysfunctions.
Moreover,
glycolytic
pathway
is
involved
different
areas
metabolism
inflammation,
associated
with
variety
transcription
factors.
To
date,
it
not
fully
elucidated
whether
changes
its
key
enzymes
onset
or
OA.
This
review
summarizes
important
role
mediating
inducing
tissue
inflammation
injury,
aim
providing
further
insights
into
pathological
functions
proposing
new
targets
for
treatment
