Drug Design Development and Therapy,
Год журнала:
2025,
Номер
Volume 19, С. 1595 - 1608
Опубликована: Март 1, 2025
Specnuezhenide
(SPN)
is
an
iridoid
glycoside
isolated
from
Fructus
Ligustri
Lucidi,
herb
prescribed
for
the
treatment
of
senile
osteoporosis.
However,
direct
role
SPN
on
bone
metabolism
remains
unclear.
In
this
study,
effects
d-galactose
(d-gal)-induced
mice,
marrow
mesenchymal
stem
cells
(BMSCs),
and
nuclear
factor-κB
ligand-induced
osteoclasts
were
examined.
Micro-computed
tomography
was
used
to
observe
microstructure.
Osteogenesis
examined
using
Western
blotting
alkaline
phosphatase
staining.
Osteoclastogenesis
F-actin
ring
Senescence-associated
β-galactosidase
detect
cell
senescence.
addition,
expression
Takeda
G
protein-coupled
receptor
5
(TGR5)/farnesoid
X
(FXR)
signaling
pathway-related
genes
proteins
determined
through
quantitative
real-time
polymerase
chain
reaction
immunofluorescence.
Oral
administration
improved
microstructure
in
d-gal-induced
mice
increased
mineral
density,
volume,
trabecular
thickness,
number.
also
upregulated
osteogenesis
markers
osteocalcin,
morphogenetic
protein
2,
runt-related
transcription
factor
2
downregulated
osteoclasis
tartrate-resistant
acid
phosphatase,
factor-κB,
activated
T-cells
bone.
Furthermore,
staining,
inhibited
formation,
reduced
activity
senescence-associated
vitro.
Mechanistically,
TGR5/FXR
pathway
BMSCs
osteoclasts.
The
protective
abolished
after
addition
TGR5
inhibitor
SBI-115
or
FXR
DY268.
Moreover,
could
elevate
mRNA
levels
TGR5,
FXR,
downstream
small
heterodimer
partner
alleviated
osteoporosis
senescence
by
activating
pathway.
Abstract
Regeneration
is
a
complex
process
affected
by
many
elements
independent
or
combined,
including
inflammation,
proliferation,
and
tissue
remodeling.
Stem
cells
class
of
primitive
with
the
potentiality
differentiation,
regenerate
self‐replication,
multidirectional
immunomodulatory
functions.
their
cytokines
not
only
inextricably
linked
to
regeneration
ectodermal
skin
tissues,
but
also
can
be
used
for
treatment
variety
chronic
wounds.
produce
exosomes
in
paracrine
manner.
cell
play
an
important
role
regeneration,
repair,
accelerated
wound
healing,
biological
properties
which
are
similar
stem
cells,
while
safer
more
effective.
Skin
bone
tissues
critical
organs
body,
essential
sustaining
life
activities.
The
weak
repairing
ability
leads
pronounced
impact
on
quality
patients,
could
alleviated
treatment.
However,
there
obstacles
that
trough
improved
bioavailability.
This
paper
summarizes
applications
mechanisms
healing.
We
propose
new
ways
utilizing
through
different
nanoformulations,
liposomes
nanoliposomes,
polymer
micelles,
microspheres,
hydrogels,
scaffold
microneedles,
improve
use
healing
regeneration.
Abstract
Osteoporosis
is
a
widely
observed
condition
characterized
by
the
systemic
deterioration
of
bone
mass
and
microarchitecture,
which
increases
patient
susceptibility
to
fragile
fractures.
The
intricate
mechanisms
governing
homeostasis
are
substantially
impacted
extracellular
vesicles
(EVs),
play
crucial
roles
in
both
pathological
physiological
contexts.
EVs
derived
from
various
sources
exert
distinct
effects
on
osteoporosis.
Specifically,
released
osteoblasts,
endothelial
cells,
myocytes,
mesenchymal
stem
cells
contribute
formation
due
their
unique
cargo
proteins,
miRNAs,
cytokines.
Conversely,
secreted
osteoclasts
immune
promote
resorption
inhibit
formation.
Furthermore,
use
as
therapeutic
modalities
or
biomaterials
for
diagnosing
managing
osteoporosis
promising.
Here,
we
review
current
understanding
impact
homeostasis,
including
classification
biogenesis
regulatory
present
an
overview
latest
research
progress
treating
using
EVs.
Finally,
discuss
challenges
prospects
translational
Journal of Extracellular Vesicles,
Год журнала:
2024,
Номер
13(4)
Опубликована: Апрель 1, 2024
Osteoporosis
(OP)
is
a
systematic
bone
disease
characterized
by
low
mass
and
fragile
microarchitecture.
Conventional
treatment
for
OP
has
limited
efficacy
long-term
toxicity.
Synthetic
biology
makes
bacterial
extracellular
vesicle
(BEVs)-based
therapeutic
strategies
promising
alternative
the
of
OP.
Here,
we
constructed
recombinant
probiotics
Escherichia
coli
Nissle
1917-pET28a-ClyA-BMP-2-CXCR4
(ECN-pClyA-BMP-2-CXCR4),
in
which
BMP-2
CXCR4
were
overexpressed
fusion
with
BEVs
surface
protein
ClyA.
Subsequently,
isolated
engineered
BEVs-BMP-2-CXCR4
(BEVs-BC)
therapy.
The
BEVs-BC
exhibited
great
targeting
vivo.
In
addition,
had
good
biocompatibility
remarkable
ability
to
promote
osteogenic
differentiation
BMSCs.
Finally,
synthetic
biology-based
significantly
prevented
an
ovariectomized
(OVX)
mouse
model.
conclusion,
both
bone-targeting
bone-forming
one-step
using
biology,
provides
effective
strategy
potential
industrialization.
Military Medical Research,
Год журнала:
2024,
Номер
11(1)
Опубликована: Июнь 12, 2024
Abstract
In
addition
to
its
recognized
role
in
providing
structural
support,
bone
plays
a
crucial
maintaining
the
functionality
and
balance
of
various
organs
by
secreting
specific
cytokines
(also
known
as
osteokines).
This
reciprocal
influence
extends
these
modulating
homeostasis
development,
although
this
aspect
has
yet
be
systematically
reviewed.
review
aims
elucidate
bidirectional
crosstalk,
with
particular
focus
on
osteokines.
Additionally,
it
presents
unique
compilation
evidence
highlighting
critical
function
extracellular
vesicles
(EVs)
within
bone-organ
axes
for
first
time.
Moreover,
explores
implications
crosstalk
designing
implementing
bone-on-chips
assembloids,
underscoring
importance
comprehending
interactions
advancing
physiologically
relevant
vitro
models.
Consequently,
establishes
robust
theoretical
foundation
preventing,
diagnosing,
treating
diseases
related
axis
from
perspective
cytokines,
EVs,
hormones,
metabolites.
Theranostics,
Год журнала:
2024,
Номер
14(11), С. 4198 - 4217
Опубликована: Янв. 1, 2024
The
utilization
of
extracellular
vesicles
(EVs)
in
wound
healing
has
been
well-documented.However,
the
direct
administration
free
EVs
via
subcutaneous
injection
at
sites
may
result
rapid
dissipation
bioactive
components
and
diminished
therapeutic
efficacy.Functionalized
hydrogels
provide
effective
protection,
as
well
ensure
sustained
release
bioactivity
during
process,
making
them
an
ideal
candidate
material
for
delivering
EVs.In
this
review,
we
introduce
mechanisms
by
which
accelerate
healing,
then
elaborate
on
construction
strategies
engineered
EVs.Subsequently,
discuss
synthesis
application
delivery
systems
to
enhance
complicated
healing.Furthermore,
face
wounds,
functionalized
with
specific
microenvironment
regulation
capabilities,
such
antimicrobial,
anti-inflammatory,
immune
regulation,
used
loading
EVs,
potential
approaches
addressing
these
challenges.Ultimately,
deliberate
future
trajectories
outlooks,
offering
a
fresh
viewpoint
advancement
artificial
intelligence
(AI)-energized
materials
3D
bio-printed
multifunctional
hydrogel-based
dressings
biomedical
applications.
Journal of Pineal Research,
Год журнала:
2024,
Номер
76(3)
Опубликована: Апрель 1, 2024
Abstract
Osteoporosis
(OP)
is
a
severe
global
health
issue
that
has
significant
implications
for
productivity
and
human
lifespan.
Gut
microbiota
dysbiosis
been
demonstrated
to
be
closely
associated
with
OP
progression.
Melatonin
(MLT)
an
important
endogenous
hormone
modulates
bone
metabolism,
maintains
homeostasis,
improves
Multiple
studies
indicated
MLT
participates
in
the
regulation
of
intestinal
gut
barrier
function.
However,
promising
effects
microbiota‐derived
remain
unclear.
Here,
we
found
resulted
tryptophan
disorder
decreased
production
MLT,
while
administration
could
mitigate
OP‐related
clinical
symptoms
reverse
dysbiosis,
including
diversity
microbiota,
relative
abundance
many
probiotics
such
as
Allobaculum
Parasutterella
,
metabolic
function
flora
amino
acid
nucleotide
energy
metabolism.
Notably,
significantly
increased
short‐chain
fatty
acids
trimethylamine
N‐oxide‐related
metabolites.
Importantly,
modulate
dynamic
balance
M1/M2
macrophages,
reduce
serum
levels
pro‐inflammatory
cytokines,
restore
gut‐barrier
Taken
together,
our
results
highlighted
roles
microbially
derived
progression
via
“gut‐bone”
axis
SCFA
which
may
provide
novel
insight
into
development
drug
treating
OP.
Cell Death Discovery,
Год журнала:
2024,
Номер
10(1)
Опубликована: Май 2, 2024
Abstract
The
escalating
threat
of
bone-related
diseases
poses
a
significant
challenge
to
human
health.
Mesenchymal
stem
cell
(MSC)-derived
extracellular
vesicles
(MSC-EVs),
as
inherent
cell-secreted
natural
products,
have
emerged
promising
treatments
for
diseases.
Leveraging
outstanding
features
such
high
biocompatibility,
low
immunogenicity,
superior
biological
barrier
penetration,
and
extended
circulating
half-life,
MSC-EVs
serve
potent
carriers
microRNAs
(miRNAs),
long
no-code
RNAs
(lncRNAs),
other
biomolecules.
These
cargo
molecules
play
pivotal
roles
in
orchestrating
bone
metabolism
vascularity
through
diverse
mechanisms,
thereby
contributing
the
amelioration
Additionally,
engineering
modifications
enhance
bone-targeting
ability
MSC-EVs,
mitigating
systemic
side
effects
bolstering
their
clinical
translational
potential.
This
review
comprehensively
explores
mechanisms
which
regulate
disease
progression.
It
delves
into
therapeutic
potential
adept
drug
carriers,
augmented
by
engineered
modification
strategies
tailored
osteoarthritis
(OA),
rheumatoid
arthritis
(RA),
osteoporosis,
osteosarcoma.
In
conclusion,
exceptional
promise
exhibited
positions
them
an
excellent
solution
with
considerable
applications
orthopedics.
