Abstract
The
gut‐bone
axis
is
a
promising
target
for
osteoporosis
treatment,
yet
existing
delivery
systems
lack
precise
targeting.
Herein,
an
oral
hydrogel
microsphere
system
(E7‐Lipo@Alg/Cs)
developed
using
gas
microfluidic
and
ionic
crosslinking
technologies
to
deliver
drugs
bone
marrow
mesenchymal
stem
cells
(BMSCs)
via
the
axis,
regulating
mitochondrial
aging.
A
BMSC‐affine
peptide
conjugated
onto
liposomes
encapsulating
Fisetin,
followed
by
incorporation
into
alginate‐calcium
microspheres.
Chitosan
electrostatically
adsorbed
surface,
creating
core‐shell
structure
that
adheres
intestinal
epithelial
cells,
withstands
gastric
acid,
facilitates
targeted
BMSCs
through
intestinal‐bone
axis.
In
vitro,
effectively
enhances
function
reverses
BMSC
aging,
while
in
vivo
studies
demonstrate
prolonged
drug
activity,
restored
osteogenic
differentiation,
regeneration.
RNA‐seq
indicates
activation
of
AMPK‐SIRT1
pathway,
reversing
aging
promoting
aged
tissue
This
provides
efficient
strategy
preventing
loss,
offering
significant
clinical
potential
treatment.
Journal of Cellular and Molecular Medicine,
Год журнала:
2025,
Номер
29(4)
Опубликована: Фев. 1, 2025
ABSTRACT
Osteoarthritis
presents
a
significant
clinical
challenge
due
to
its
high
prevalence
and
the
resultant
impairment
of
patients'
motor
function.
Osteoarthritic
chondrocytes
are
characterised
by
inflammation
metabolic
disturbances.
Pioglitazone,
an
agonist
peroxisome
proliferator‐activated
receptor
γ
(PPAR‐γ),
has
been
demonstrated
exert
anti‐inflammatory
effects
across
various
diseases.
This
study
aims
investigate
potential
protective
Pioglitazone
on
osteoarthritic
chondrocytes.
An
in
vitro
chondrocyte
model
was
established
utilising
IL‐1β.
The
impact
extracellular
matrix
synthesis
evaluated
through
enzyme‐linked
immunosorbent
assay,
immunofluorescence
staining
Alcian
blue
staining.
affinity
for
PPAR‐γ
investigated
using
molecular
docking
techniques.
Alterations
glycolysis
oxidative
phosphorylation
were
examined
Seahorse
XF
Analyser,
influence
glucose
uptake
mitochondrial
electron
transport
chain
further
analysed.
gavaged
mouse
OA
anterior
cruciate
ligament
transection
evaluate
therapeutic
efficacy
Pioglitazone.
Our
findings
indicate
that
mitigates
osteoarthritis
murine
models
inhibiting
expression
inflammatory
mediators
such
as
TNF‐α,
IL‐6
PGE2,
preventing
degradation
aggrecan
collagen
II.
Furthermore,
significantly
upregulated
transporter
1
stabilised
proton
delivery
PPAR‐γ‐dependent
manner,
thereby
enhancing
uptake,
glycolysis,
phosphorylation.
These
partially
reversed
antagonist
GW9662.
can
confer
chondroprotective
benefits
activating
PPAR‐γ.
Journal of Multidisciplinary Healthcare,
Год журнала:
2025,
Номер
Volume 18, С. 1353 - 1369
Опубликована: Март 1, 2025
Osteoarthritis
(OA)
is
a
chronic
and
complex
degenerative
joint
disease
that
increasingly
burdens
affects
the
elderly
population.
Abnormal
energy
metabolism
closely
associated
with
pathological
mechanisms
of
OA.
This
study
aims
to
identify
key
genes
related
are
linked
treatment
diagnosis
The
transcriptomic
data
for
OA
were
collected
from
Gene
Expression
Omnibus
(GEO),
GSE51588
GSE63359
serving
as
training
validation
datasets,
respectively.
Differential
expression
analysis
was
conducted
metabolism-related
genes.
Unsupervised
clustering
performed
classify
molecular
subtypes.
Three
machine
learning
algorithms
employed
genes,
specifically
Least
Absolute
Shrinkage
Selection
Operator
(LASSO),
Support
Vector
Machine
Recursive
Feature
Elimination
(SVM-RFE),
Random
Forest
(RF).
We
construct
comprehensive
nomogram,
diagnostic
performance
both
nomogram
feature
evaluated
using
operating
characteristic
curve
(ROC)
calibration
curves.
assessed
immune
infiltration
levels
in
samples
IOBR
platform
CIBERSORT
algorithm.
classified
patients
into
two
subtypes,
which
exhibited
distinct
differences
levels.
Subsequently,
we
successfully
identified
NUP98
RPIA,
demonstrated
statistically
significant
(P
<
0.05)
cohort.
Evaluation
ROC
curves
these
exhibit
robust
performance.
Multiple
cells
may
be
involved
development
OA,
all
varying
degrees.
In
conclusion,
RPIA
have
potential
serve
biomarkers
offer
opportunities
therapeutic
intervention
Redox Biology,
Год журнала:
2025,
Номер
83, С. 103667 - 103667
Опубликована: Май 8, 2025
Mitochondria
are
essential
regulators
of
bone
health,
controlling
cell
differentiation,
cellular
energy
production,
immune
function,
osteogenesis,
and
osteoclast
activity.
Their
dysfunction
is
linked
to
orthopedic
disorders
such
as
osteoporosis,
osteoarthritis,
osteomyelitis,
contributing
impaired
homeostasis
increased
fracture
risk.
While
mitochondrial
research
has
been
more
advanced
in
fields
cardiology
neurology,
emerging
therapeutic
strategies
from
these
areas
beginning
show
potential
for
translation
into
orthopedics.
These
include
biogenesis
stimulation,
fission
inhibition,
antioxidant
therapies,
transplantation,
photobiomodulation,
which
have
demonstrated
success
enhancing
tissue
repair,
reducing
oxidative
stress,
improving
overall
function
non-orthopedic
applications.
The
novel
inhibitor
accumulation
reactive
oxygen
species
Mdivi-1
offers
improve
clinical
outcomes
diseases
by
alleviating
preventing
loss.
treatments
still
the
developmental
phase,
they
present
innovative
approaches
address
conditions,
potentially
transforming
disease
management
patient
outcomes.
This
report
explores
regarding
involvement
health
joint
discusses
possible
future
treatment
targeting
mitochondria
conditions.
