bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Ноя. 6, 2024
Abstract
Aging
predisposes
individuals
to
reduced
bone
mass
and
fragility
fractures,
which
are
costly
linked
high
mortality.
Understanding
how
aging
affects
fracture
healing
is
essential
for
developing
therapies
enhance
regeneration
in
older
adults.
During
the
inflammatory
phase
of
healing,
immune
cells
recruited
injury
site
as
periosteal
skeletal
stem/progenitor
(pSSPCs)
rapidly
proliferate
differentiate
into
osteochondral
lineages,
allowing
fibrocartilaginous
callus
formation
complete
healing.
Irrespective
age,
mesenchymal
interact
during
early
incompletely
understood,
limiting
our
ability
potentially
modulate
these
processes.
To
address
this,
we
directly
analyzed,
parallel,
at
a
single-cell
level,
isolated
murine
CD45(+)
CD45(-)
dissected
from
intact
fractured
bones,
collected
three
days
after
injury.
Through
comprehensive
analysis,
corroborated
by
bulk
RNA-sequencing,
flow
cytometry,
histology,
found
decreases
pSSPCs
proliferative,
marked
expression
genes
required
an
increased
senescence
signature.
We
that
chemokine
Cxcl9
was
highly
upregulated
aged
Prrx1+
pSSPCs,
predicted
with
other
directly,
associated
recruitment
CD8+
T
Cell-to-cell
communication
analysis
provided
insight
complexity
interactions
among
many
cell
types
regulating
impact
on
Together,
results
provide
age-induced
alterations
informing
development
improved
therapeutic
approaches
fractures.
We
present
a
transcriptomic
analysis
that
provides
better
understanding
of
regulatory
mechanisms
within
the
healthy
and
injured
periosteum.
The
focus
this
work
is
on
characterizing
early
events
controlling
bone
healing
during
formation
periosteal
callus
day
3
after
fracture.
Building
our
previous
findings
showing
induced
Notch1
signaling
in
osteoprogenitors
leads
to
healing,
we
compared
samples
which
Notch
1
intracellular
domain
overexpressed
by
stem/progenitor
cells,
with
control
intact
fractured
Molecular
changes
skeletal
cells
(SSPCs)
other
cell
populations
callus,
including
hematopoietic
lineages,
were
determined.
Notably,
ligands
differentially
expressed
endothelial
mesenchymal
populations,
Dll4
restricted
whereas
Jag1
was
populations.
Targeted
deletion
using
Cdh5CreER
resulted
negative
effects
fracture
while
SSPCs
α-smooth
muscle
actin-CreER
did
not
impact
healing.
Translating
these
observations
into
clinically
relevant
model
revealed
beneficial
delivering
alongside
osteogenic
inducer,
BMP2.
These
provide
insights
periosteum,
paving
way
for
novel
translational
approaches
Journal of Clinical Investigation,
Год журнала:
2024,
Номер
134(17)
Опубликована: Сен. 2, 2024
The
periosteum
contains
skeletal
stem/progenitor
cells
that
contribute
to
bone
fracture
healing.
However,
the
in
vivo
identity
of
periosteal
stem
(P-SSCs)
remains
unclear,
and
membrane
protein
markers
P-SSCs
facilitate
tissue
engineering
are
needed.
Here,
we
identified
integral
2A
(Itm2a)
enriched
SSCs
using
single-cell
transcriptomics.
Itm2a+
displayed
clonal
multipotency
self-renewal
sat
at
apex
their
differentiation
hierarchy.
Lineage-tracing
experiments
showed
Itm2a
selectively
labeled
were
preferentially
located
outer
fibrous
layer
periosteum.
rarely
expressed
CD34
or
Osx,
but
such
as
Ctsk,
CD51,
PDGFRA,
Sca1,
Gli1.
contributed
osteoblasts,
chondrocytes,
marrow
stromal
upon
injury.
Genetic
lineage
tracing
dual
recombinases
Prrx1
generated
spatially
separated
subsets
chondrocytes
osteoblasts
during
Bone
morphogenetic
2
(Bmp2)
deficiency
ablation
resulted
defects
ITM2A+
also
present
human
Thus,
our
study
a
marker
labels
P-SSCs,
providing
an
attractive
target
for
drug
cellular
therapy
disorders.
Cell Reports,
Год журнала:
2025,
Номер
44(5), С. 115620 - 115620
Опубликована: Май 1, 2025
Hematopoietic
stem
cells
(HSCs)
generating
all
blood
are
maintained
by
their
niche
cells,
termed
CXCL12-abundant
reticular
(CAR)
which
strongly
overlap
with
leptin-receptor-expressing
(LepR+)
in
the
bone
marrow.
A
meta-analysis
of
single-cell
RNA
sequencing
datasets
across
tissues
hypothesized
that
universal
fibroblasts
present
organs
give
rise
to
distinct
tissue-specific
fibroblast
subsets
designated
as
specialized
fibroblasts,
including
CAR/LepR+
cells.
However,
there
is
no
direct
evidence
can
differentiate
into
at
a
distant
location.
Here,
we
demonstrated
CD248+
from
lung
and
colon
outside
skeletal
system,
well
muscle,
generated
characterized
HSC
functions
expression
cytokines
transcription
factors
essential
for
maintenance
during
ectopic
formation
or
after
intra-bone
marrow
transplantation.
These
results
demonstrate
potential
marrow-specific
scattered
throughout
entire
body.
Bone,
Год журнала:
2024,
Номер
190, С. 117315 - 117315
Опубликована: Ноя. 4, 2024
Tissue
engineering
employs
the
use
of
bioactive
materials
to
facilitate
filling
and
acceleration
bone
defect
healing,
thereby
introducing
novel
concepts
field
in
situ
repair.
Some
studies
have
shown
that
periosteum
plays
an
important
role
regeneration
In
this
study,
biomimetic
periosteum-bone
scaffolds
were
prepared
by
depositing
poly-L-lactic
acid
(PLLA)
electrospun
fibers
on
surface
gelatin/chitosan
cryogel
mimic
structure,
respectively.
To
improve
bioactivity
scaffold,
morphogenetic
protein-2
(BMP-2)
was
loaded
into
a
loose
porous
mesh-like
cryogel,
while
platelet-derived
growth
factor-BB
(PDGF-BB)
encapsulated
core
PLLA
nanofibers
with
core-shell
structure.
Both
these
two
factors
released
locally
at
site
defect,
where
they
exert
synergistic
effect
osteogenesis,
greatly
accelerating
healing.
The
vitro
experiments
demonstrated
exhibited
favourable
biocompatibility
osteogenesis
ability.
Furthermore,
vivo
indicated
composite
scaffold
repaired
rat
skull
defects
more
rapid
effective
manner.
conclusion,
codelivery
BMP-2
PDGF-BB
shows
significant
potential
for
regeneration.
Advanced Functional Materials,
Год журнала:
2024,
Номер
unknown
Опубликована: Дек. 11, 2024
Abstract
With
the
improvement
of
implant
design
and
expansion
application
scenarios,
orthopedic
implants
have
become
a
common
surgical
option
for
treating
fractures
end‐stage
osteoarthritis.
Their
goal
is
rapidly
forming
long‐term
stable
osseointegration.
However,
this
fixation
effect
limited
by
surface
characteristics
peri‐implant
bone
tissue
activity.
Therefore,
review
summarizes
strategies
interface
engineering
(osteogenic
peptides,
growth
factors,
metal
ions)
treatment
methods
(porous
nanotubes,
hydrogel
embedding,
other
load‐release
systems)
through
research
on
its
biological
mechanism,
paving
way
to
achieve
adaptation
both
coordination
between
different
strategies.
transition
osseointegration
stage,
demonstrated
varying
therapeutic
effects.
Especially,
activity
osteoblasts
runs
almost
entire
process
osseointegration,
their
physiological
activities
play
dominant
role
in
formation.
Furthermore,
diseases
impacting
metabolism
exacerbate
difficulty
achieving
This
aims
assist
future
improve
implant‐bone
fixation,
promote
fracture
healing,
enhance
post‐implantation
recovery.
