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.
Journal of Bone and Mineral Research,
Год журнала:
2024,
Номер
unknown
Опубликована: Апрель 30, 2024
Abstract
Bone
development,
growth,
and
repair
are
complex
processes
involving
various
cell
types
interactions,
with
central
roles
played
by
skeletal
stem
progenitor
cells.
Recent
research
brought
new
insights
into
the
precursor
populations
that
mediate
intramembranous
endochondral
bone
development.
Later
in
life,
many
of
cellular
molecular
mechanisms
determining
development
reactivated
upon
fracture,
powerful
trauma-induced
signaling
cues
triggering
a
variety
postnatal
stem/progenitor
cells
(SSPCs)
residing
near
defect.
Interestingly,
this
injury
context,
current
evidence
suggests
fates
both
SSPCs
differentiated
can
be
considerably
flexible
dynamic,
multiple
sources
activated
to
operate
as
functional
progenitors
generating
chondrocytes
and/or
osteoblasts.
The
combined
implementation
vivo
lineage
tracing,
surface
marker-based
selection,
single-cell
analyses,
high-resolution
situ
imaging
has
strongly
improved
our
diversity
developmental
reparative
subsets,
while
also
unveiling
complexity
their
dynamics,
hierarchies,
relationships.
Albeit
incompletely
understood
at
present,
findings
supporting
flexibility
possibly
plasticity
among
osteogenic
challenge
classical
dogma
single
primitive,
self-renewing,
multipotent
driving
tissue
formation
regeneration
from
apex
hierarchical
strictly
unidirectional
differentiation
tree.
We
here
review
state
field
newest
discoveries
origin,
identity,
during
discuss
contributions
adult
SSPC
fracture
repair,
reflect
on
dynamism
relationships
precursors
lineages.
Further
directed
unraveling
heterogeneity
capacities
SSPCs,
well
regulatory
fate
functioning,
will
offer
vital
options
for
clinical
translation
toward
compromised
healing
regenerative
medicine.
Scientific Reports,
Год журнала:
2024,
Номер
14(1)
Опубликована: Май 3, 2024
Abstract
Hydrolyzed
egg
yolk
peptide
(YPEP)
was
shown
to
increase
bone
mineral
density
in
ovariectomized
rats.
However,
the
underlying
mechanism
of
YPEP
on
osteoporosis
has
not
been
explored.
Recent
studies
have
that
Wnt/β-catenin
signaling
pathway
and
gut
microbiota
may
be
involved
regulation
metabolism
progression
osteoporosis.
The
present
study
aimed
explore
preventive
effect
supplementation
(OVX)
rats
verify
whether
can
improve
by
regulating
microbiota.
experiment
included
five
groups:
sham
surgery
group
(SHAM),
ovariectomy
(OVX),
17-β
estradiol
(E2:
25
µg
/kg/d
17β-estradiol),
OVX
with
low-dose
(LYPEP:
10
mg
YPEP)
high-dose
(HYPEP:
40
YPEP).
In
this
study,
all
samples
used
were
femurs.
Micro-CT
analysis
revealed
improvements
both
(BMD)
microstructure
treatment.
three-point
mechanical
bending
test
indicated
an
enhancement
biomechanical
properties
groups.
serum
levels
alkaline
phosphatase
(BALP),
gla
protein
(BGP),
calcium
(Ca),
phosphorus
(P)
markedly
higher
groups
than
group.
LYPEP
had
lower
(ALP),
tartrate-resistant
acid
(TRAP)
C-terminal
telopeptide
type
I
collagen
(CTX-I)
significantly
Wnt3a,
β-catenin,
LRP5,
RUNX2
OPG
compared
Compared
group,
ratio
OPG/RANKL
At
genus
level,
there
a
relative
abundance
Lachnospiraceae_NK4A136_group
decrease
Escherichia_Shigella
groups,
correlation
analysis,
no
between
these
two
bacteria
indexes.
These
findings
demonstrate
potential
osteoporosis,
associated
its
modulating
pathway.
Skeletal
stem
cells
(SSCs)
reside
in
various
niche
locations
within
long
bones
to
maintain
bone
homeostasis
and
facilitate
fracture
repair.
Bone
fragility,
associated
with
ageing,
increases
the
susceptibility
of
femoral
head
fractures
due
an
increase
adipocytes
concomitant
loss
structural
integrity.
However,
specific
contribution
epiphyseal
SSCs
fragility
is
unknown.
To
explore
this,
a
comparative
analysis
was
performed
on
transcriptional
profiles
lineage
commitment
Wistar
rat
derived
from
marrow
(BM-),
diaphyseal
cortical
(CB-)
proximal
trabecular
(PF-SSCs)
isolated
same
bones.
were
characterized
based
morphology,
immunophenotype
(CD90/CD45),
growth
rate
(population
doubling
time),
gene
expression
differentiation
capacity
(Oil
Red
O,
Alizarin
S).
qRT-PCR
micro-arrays
evaluate
stemness,
SSC
lineage-specific
markers
both
undifferentiated
differentiated
states.
Our
findings
support
hypothesis
that
different
regions
exhibit
distinct
profiles,
reflecting
their
environments.
CB-SSCs
displayed
superior
osteogenic
potential
as
evidenced
by
key
genes
higher
levels
mineralization.
In
contrast,
PF-SSCs
had
reduced
adipogenic
potential.
Overall,
study
revealed
importance
niche-specific
cell
properties
for
use
regenerative
medicine
applications
provides
insight
into
role
risk.
Cellular and Molecular Life Sciences,
Год журнала:
2025,
Номер
82(1)
Опубликована: Март 11, 2025
The
bone
marrow
microenvironment
contains
heterogeneous
stromal
cells,
which
are
critical
for
remodeling
and
provide
essential
supportive
roles
hematopoietic
functions.
Although
the
diversity
of
PDGFRα+β+
mesenchymal
stromal/stem
cells
(MSCs)
get
consensus,
osteo-lineage
(OLCs)
that
constitute
developmental
trajectory
osteoblasts
largely
remain
unclear.
Here,
we
construct
a
comprehensive
atlas
cell
via
performing
integrative
single
analyses
77
samples
from
14
datasets.
Besides
previously
defined
Lepr+
BM-MSCs
derived
OLC1,
present
novel
OLC2
with
unique
molecular
signatures
differentiation
pathway.
Both
OLC1
show
significant
polygenic
association
mineral
density
(BMD),
while
extracellular
matrix
(ECM)
proteins
specifically
expressed
by
particularly
decreased
in
tissue
aged
mice.
Notably,
consistently
reduced
mice,
might
be
induced
expression
several
lineage
drivers.
Collectively,
our
study
presents
thorough
prospect
OLCs
highlights
their
important
age-related
osteoporosis.
Proceedings of the National Academy of Sciences,
Год журнала:
2025,
Номер
122(12)
Опубликована: Март 17, 2025
The
mandible,
also
known
as
the
lower
jaw,
is
only
bone
in
skull
that
can
move
and
essential
for
speaking
chewing.
Meckel’s
cartilage
(MC)
a
temporary
structure
supports
formation
of
but
how
MC
involved
ossification
mandible
poorly
understood.
Through
use
single-cell
RNA
sequencing
spatial
transcriptomics
analyses,
spatiotemporal
atlas
human
fetuses
from
7
to
15
wk
postconception
was
established,
highlighting
role
mandible.
Importantly,
we
revealed
two
populations
contributed
mandibular
through
different
mechanisms.
anterior
differentiate
into
osteolineage
cells,
shown
an
vivo
lineage
tracing
mouse
model.
intermediate
facilitates
intramembranous
cell–cell
communications,
possibly
signaling
ligands
like
BMP5
,
BMP7
SEMA3A
PDGFC
FGF7
.
This
study
suggests
plays
crucial
mediating
distinct
mechanisms,
providing
valuable
insights
understanding
oral
craniofacial
diseases
disorders
future.
