Osteoporosis
presents
a
marked
global
public
health
challenge,
characterized
by
deficient
osteogenesis
and
deteriorating
immune
microenvironment.
Conventional
clinical
interventions
primarily
target
osteoclast-mediated
bone
damage,
yet
lack
comprehensive
therapeutic
approach
that
balances
formation
resorption.
Herein,
we
introduce
bone-targeted
nanocomposite,
A-Z@Pd(H),
designed
to
address
these
challenges
integrating
diverse
functional
components.
The
nanocomposite
incorporates
internal
hydrogen-carrying
nanozymes,
which
effectively
scavenge
multiple
reactive
oxygen
species
(ROS)
synergistically
engage
the
autophagy–lysosome
pathway
accelerate
endogenous
ROS
degradation
in
macrophages.
This
mechanism
disrupts
vicious
cycle
of
autophagic
dysfunction–ROS
accumulation–macrophage
inflammation.
In
addition,
external
metal–organic
frameworks
release
zinc
ions
(Zn
2+
)
response
acidic
osteoporotic
environment,
thereby
promoting
osteogenesis.
murine
model
osteoporosis,
intravenous
administration
A-Z@Pd(H)
leads
preferential
accumulation
femur,
remodeling
microenvironment
through
regulation,
promotion,
osteoclast
inhibition.
These
findings
suggest
this
system
composed
hydrogen
therapy
ion
may
be
promising
candidate
for
osteoporosis.
Bioactive Materials,
Journal Year:
2023,
Volume and Issue:
27, P. 138 - 153
Published: March 30, 2023
Osteoclasts
ubiquitously
participate
in
bone
homeostasis,
and
their
aberration
leads
to
diseases,
such
as
osteoporosis.
Current
clinical
strategies
by
biochemical
signaling
molecules
often
perturb
innate
metabolism
owing
the
uncontrolled
management
of
osteoclasts.
Thus,
an
alternative
strategy
precise
regulation
for
osteoclast
differentiation
is
urgently
needed.
To
this
end,
study
proposed
assumption
that
mechanic
stimulation
might
be
a
potential
strategy.
Here,
hydrogel
was
created
imitate
physiological
microenvironment,
with
stiffnesses
ranging
from
2.43kPa
68.2kPa.
The
impact
matrix
stiffness
on
behaviors
thoroughly
investigated.
Results
showed
could
harnessed
directing
fate
vitro
vivo.
In
particular,
increased
inhibited
integrin
β3-responsive
RhoA-ROCK2-YAP-related
mechanotransduction
promoted
osteoclastogenesis.
Notably,
preosteoclast
development
facilitated
medium-stiffness
(M-gel)
possessing
same
vessel
17.5
kPa
44.6
partial
suppression
mechanotransduction,
which
subsequently
encouraged
revascularization
regeneration
mice
defects.
Our
works
provide
innovative
approach
finely
regulating
selecting
optimum
enable
us
further
develop
stiffness-based
tissue
engineering.
Cell Death and Disease,
Journal Year:
2024,
Volume and Issue:
15(2)
Published: Feb. 12, 2024
Abstract
Histone
methylation
plays
a
crucial
role
in
various
cellular
processes.
We
previously
reported
the
vitro
function
of
histone
lysine
demethylase
7
A
(KDM7A)
osteoblast
and
adipocyte
differentiation.
The
current
study
was
undertaken
to
investigate
physiological
KDM7A
bone
homeostasis
elucidate
underlying
mechanisms.
conditional
strategy
employed
delete
Kdm7a
gene
specifically
osterix-expressing
osteoprogenitor
cells
mice.
resulting
mutant
mice
exhibited
significant
increase
cancellous
mass,
accompanied
by
an
osteoblasts
formation,
as
well
reduction
osteoclasts,
marrow
adipocytes
resorption.
stromal
(BMSCs)
calvarial
pre-osteoblastic
derived
from
enhanced
osteogenic
differentiation
suppressed
adipogenic
Additionally,
osteoclastic
precursor
impaired
osteoclast
Co-culturing
BMSCs
with
wild-type
resulted
inhibition
Mechanistic
investigation
revealed
that
able
upregulate
expression
fibroblast
activation
protein
α
(FAP)
receptor
activator
nuclear
factor
κB
ligand
(RANKL)
through
removing
repressive
di-methylation
marks
H3K9
H3K27
Fap
Rankl
promoters.
Moreover,
recombinant
FAP
attenuated
dysregulation
deficient
Finally,
deficiency
prevented
ovariectomy-induced
loss
This
establish
its
epigenetic
regulation
Consequently,
inhibiting
may
prove
beneficial
ameliorating
osteoporosis.
Journal of the mechanical behavior of biomedical materials/Journal of mechanical behavior of biomedical materials,
Journal Year:
2024,
Volume and Issue:
157, P. 106661 - 106661
Diabetes
exacerbates
periodontitis
by
overexpressing
reactive
oxygen
species
(ROS),
which
leads
to
periodontal
bone
resorption.
Consequently,
it
is
imperative
relieve
inflammation
and
promote
alveolar
regeneration
comprehensively
for
the
development
of
diabetic
treatment
strategies.
Furthermore,
an
orderly
avoid
interference
between
these
two
processes
can
achieve
optimal
therapeutic
effect.
Thus,
we
constructed
a
sequential
sustained
release
system
based
on
zeolitic
imidazolate
framework-8
(ZIF-8)-modified
chitosan
thermosensitive
hydrogel
(TOOTH)
therapy
in
this
work.
Chemically
modified
tetracycline-3
(CMT-3)
platelet-derived
growth
factor-BB
(PDGF-BB)
were
loaded
ZIF-8
release,
respectively,
with
aim
reducing
facilitating
tissue
regeneration.
During
therapy,
CMT-3
first
escaped
from
due
degradation
diffusion
ROS
elimination.
Subsequently,
was
dissociated
under
acid
microenvironment,
PDGF-BB
sustainably
released
osteogenesis.
The
intervals
could
be
regulated
sizes
ZIF-8.
biocompatible
TOOTH
exhibited
favorable
effect
vitro
vivo.
sequentially
controlled
facilitated
holds
promise
promoting
offers
potential
clinical
translation.
