bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2023,
Volume and Issue:
unknown
Published: Aug. 14, 2023
Abstract
Ectopic
bone
marrow
adipocytes
(BMAds)
accumulation
occurring
under
diverse
pathophysiological
conditions
leads
to
deterioration.
Estrogen-related
receptor
α
(ESRRA)
is
a
key
regulator
responding
metabolic
stress.
Here,
we
show
that
adipocyte-specific
ESRRA
deficiency
rescues
osteogenesis
and
vascular
formation
in
adipocyte-rich
due
estrogen
or
obesity.
Mechanistically,
adipocyte
interferes
with
E2/ESR1
signaling
resulting
transcriptional
repression
of
secreted
phosphoprotein
1
(
Spp1
);
positively
modulates
Leptin
expression
by
binding
its
promoter.
abrogation
results
enhanced
SPP1
decreased
LEPTIN
secretion
from
both
visceral
BMAds,
concertedly
dictating
stromal
stem
cell
fate
commitment
restoring
type
H
vessel
formation,
constituting
feed-forward
loop
for
formation.
Pharmacological
inhibition
protects
obese
mice
against
loss
high
adiposity.
Thus,
our
findings
highlight
therapeutic
approach
via
targeting
preserve
especially
detrimental
milieu.
Graphic
abstract
Frontiers in Immunology,
Journal Year:
2024,
Volume and Issue:
15
Published: Oct. 23, 2024
Introduction
Open
reduction
and
fixation
are
the
standard
of
care
for
treating
mandibular
fractures
usually
lead
to
successful
healing.
However,
complications
such
as
delayed
healing,
non-union,
infection
can
compromise
patient
outcomes
increase
healthcare
costs.
The
initial
inflammatory
response,
particularly
response
involving
specific
CD8
+
T
cell
subpopulations,
is
thought
play
a
critical
role
in
healing
long
bone
fractures.
In
this
study,
we
investigated
these
immune
profiles
patients
with
impaired
Materials
methods
prospective
included
surgically
treated
at
Charité
–
Universitätsmedizin
Berlin,
Germany,
between
September
2020
December
2022.
We
used
follow-up
imaging
clinical
assessment
evaluate
addition,
analyzed
using
flow
cytometry
quantified
cytokine
levels
electrochemiluminescence-based
multiplex
immunoassays
preoperative
blood
samples.
Results
Out
55
enrolled,
38
met
inclusion
criteria
(30
men
8
women;
mean
age
32.18
years).
Radiographic
evaluation
revealed
31
cases
normal
7
incomplete
consolidation,
including
1
case
non-union.
Patients
exhibited
increased
terminally
differentiated
effector
memory
cells
(T
EMRA
)
higher
regulatory
reg
ratio,
compared
those
Conclusions
Our
analysis
fracture
confirms
our
hypothesis
derived
from
healing:
monitoring
ratio
be
an
early
indicator
risk
Radiologic
enabled
us
detect
that
might
not
detected
by
only.
This
study
highlights
potential
individual
predict
may
form
basis
future
strategies
manage
complications.
Genes,
Journal Year:
2024,
Volume and Issue:
15(12), P. 1568 - 1568
Published: Dec. 4, 2024
Background/Objectives:
Mesenchymal
stem
cells
(MSCs)
possess
the
remarkable
ability
to
differentiate
into
various
cell
types,
including
osteoblasts.
Understanding
molecular
mechanisms
governing
MSC
osteogenic
differentiation
is
crucial
for
advancing
clinical
applications
and
our
comprehension
of
complex
disease
processes.
However,
key
biological
molecules
regulating
this
process
remain
incompletely
understood.
Methods:
In
study,
we
conducted
systematic
re-analyses
published
high-throughput
transcriptomic
datasets
identify
validate
that
dynamically
regulate
differentiation.
Our
approach
involved
a
comprehensive
analysis
gene
expression
patterns
across
human
tissues,
followed
by
rigorous
experimental
validation
identified
candidates.
Results:
Through
integrated
analytical
approaches,
utilized
transcriptomics
four
critical
regulators
differentiation:
PTBP1,
H2AFZ,
BCL6,
TTPAL
(C20ORF121).
Among
these,
PTBP1
H2AFZ
functioned
as
positive
regulators,
while
BCL6
acted
negative
in
osteogenesis.
The
regulatory
roles
these
genes
osteogenesis
were
further
validated
via
overexpression
experiments.
Conclusions:
findings
advance
understanding
fate
determination
open
new
therapeutic
possibilities
bone-related
disorders.
identification
provides
foundation
developing
targeted
interventions
regenerative
medicine.
Acta Biomaterialia,
Journal Year:
2024,
Volume and Issue:
192, P. 260 - 278
Published: Dec. 12, 2024
Regeneration
of
large
bone
defects
remains
a
clinical
challenge
until
today.
While
existing
biomaterials
are
predominantly
addressing
healing
via
direct,
intramembranous
ossification
(IO),
tissue
formation
cartilage
phase,
so-called
endochondral
(EO)
has
been
shown
to
be
promising
alternative
strategy.
However,
pure
biomaterial
approaches
for
EO
induction
sparse
and
the
knowledge
how
material
components
can
have
bioactive
contribution
required
is
limited.
Here,
we
combined
previously
developed
purely
architecture-driven
approach
with
release
therapeutic
metal
ions
from
tailored
silicate
microparticles.
The
delivery
platform
was
free
calcium
phosphates
(CaP)
that
known
support
IO
but
not
employed
lithium
(Li),
magnesium
(Mg),
strontium
(Sr)
or
zinc
(Zn)
ions.
We
identified
an
ion-specific
cellular
response
in
which
certain
strongly
enhanced
cell
recruitment
into
showed
superior
chondrogenesis
deposition
collagen
II
by
human
mesenchymal
stromal
cells
(MSCs).
At
same
time,
some
cases
microparticle
incorporation
altered
mechanical
properties
consequences
cell-induced
contraction
scaffold
wall
deformation.
Collectively,
results
suggest
metal-doped
microparticles
potential
further
improve
bioactivity
architectured
defect
EO.
STATEMENT
OF
SIGNIFICANCE:
Endochondral
healing,
process
resembles
embryonic
skeletal
development,
gained
prominence
regenerative
medicine.
most
strategies
optimized
instead
target
direct
through
IO.
report
on
novel
accelerate
biomaterial-guided
combining
cell-guiding
scaffolds
other
strategies,
such
as
hypoxia-mimic
drugs
iron-chelating
biomaterials,
documented
literature
before
enhance
EO,
our
uniquely
implements
strategy
regeneration.
Enhanced
more
pronounced
were
observed
specific
hybrid
formulations,
suggesting
high
relevance
this
new
improved
healing.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2023,
Volume and Issue:
unknown
Published: Aug. 14, 2023
Abstract
Ectopic
bone
marrow
adipocytes
(BMAds)
accumulation
occurring
under
diverse
pathophysiological
conditions
leads
to
deterioration.
Estrogen-related
receptor
α
(ESRRA)
is
a
key
regulator
responding
metabolic
stress.
Here,
we
show
that
adipocyte-specific
ESRRA
deficiency
rescues
osteogenesis
and
vascular
formation
in
adipocyte-rich
due
estrogen
or
obesity.
Mechanistically,
adipocyte
interferes
with
E2/ESR1
signaling
resulting
transcriptional
repression
of
secreted
phosphoprotein
1
(
Spp1
);
positively
modulates
Leptin
expression
by
binding
its
promoter.
abrogation
results
enhanced
SPP1
decreased
LEPTIN
secretion
from
both
visceral
BMAds,
concertedly
dictating
stromal
stem
cell
fate
commitment
restoring
type
H
vessel
formation,
constituting
feed-forward
loop
for
formation.
Pharmacological
inhibition
protects
obese
mice
against
loss
high
adiposity.
Thus,
our
findings
highlight
therapeutic
approach
via
targeting
preserve
especially
detrimental
milieu.
Graphic
abstract
