bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2023,
Номер
unknown
Опубликована: Ноя. 16, 2023
Abstract
Although
elderly
osteoporotic
patients
have
similar
implant
survival
rates
compared
to
those
of
normal
individuals,
they
require
longer
healing
periods
achieve
proper
osseointegration.
This
may
be
related
chronic
inflammatory
responses
and
impaired
stem
cell
repair
functions
in
the
bone
microenvironment.
Recently,
deubiquitinating
enzyme,
ubiquitin-specific
peptidase
7
(USP7),
was
found
regulate
macrophage
immune
response
modulate
osteogenic
differentiation.
The
selective
inhibitor
USP7,
P5091,
has
also
been
promote
homeostasis
conditions.
However,
roles
USP7
P5091
osteoimmunology
dental
osseointegration
under
senile
conditions
remain
unclear.
In
this
study,
depletion
were
showed
inhibit
inflammation
senescent
marrow
derived
macrophages
(BMDMs)
differentiation
aged
BMSCs.
Furthermore,
mRNA-Seq
revealed
that
could
enhance
efferocytosis
BMDMs
through
EPSIN1/
low-density
lipoprotein
receptor-related
protein
1
(LRP1)
pathway
selectively
induce
apoptosis
(senolysis)
mice,
we
period
prolonged
young
promoted
early
stage
osseointegration,
which
around
implant.
Collectively,
study
suggests
inhibition
accelerate
process
by
promoting
BMSCs
apoptosis.
implications
for
understanding
cellular
interactions
signaling
mechanisms
peri-implant
microenvironment
It
provide
clinical
significance
developing
new
therapies
quality
shorten
edentulous
patients.
Cell Proliferation,
Год журнала:
2023,
Номер
56(8)
Опубликована: Март 8, 2023
Abstract
Osteoporosis
is
an
ageing‐related
disease,
that
has
become
a
major
public
health
problem
and
its
pathogenesis
not
yet
been
fully
elucidated.
Substantial
evidence
suggests
strong
link
between
overall
age‐related
disease
progression
epigenetic
modifications
throughout
the
life
cycle.
As
important
modification,
ubiquitination
extensively
involved
in
various
physiological
processes,
role
bone
metabolism
attracted
increasing
attention.
Ubiquitination
can
be
reversed
by
deubiquitinases,
which
counteract
protein
degradation.
largest
most
structurally
diverse
cysteinase
family
of
deubiquitinating
enzymes,
ubiquitin‐specific
proteases
(USPs),
comprising
cysteine
kinase
have
found
to
players
maintaining
balance
formation
resorption.
The
aim
this
review
explore
recent
findings
highlighting
regulatory
functions
USPs
provide
insight
into
molecular
mechanisms
governing
their
actions
during
loss.
An
in‐deep
understanding
USPs‐mediated
regulation
resorption
will
scientific
rationale
for
discovery
development
novel
USP‐targeted
therapeutic
strategies
osteoporosis.
Journal of Dental Research,
Год журнала:
2024,
Номер
unknown
Опубликована: Дек. 9, 2024
Although
elderly
osteoporotic
patients
have
similar
implant
survival
rates
compared
with
those
of
normal
individuals,
they
require
longer
healing
periods
to
achieve
proper
osseointegration.
This
may
be
related
chronic
inflammatory
responses
and
impaired
stem
cell
repair
functions
in
the
bone
microenvironment.
Recently,
deubiquitinating
enzyme,
ubiquitin-specific
peptidase
7
(USP7),
was
found
regulate
macrophage
immune
response
modulate
osteogenic
differentiation.
The
selective
inhibitor
USP7,
P5091,
has
also
been
promote
homeostasis
conditions.
However,
roles
USP7
P5091
osteoimmunology
dental
osseointegration
under
senile
conditions
remain
unclear.
In
this
study,
depletion
were
shown
inhibit
inflammation
senescent
marrow-derived
macrophages
(BMDMs)
differentiation
aged
marrow
mesenchymal
stromal
cells
(BMSCs).
Furthermore,
mRNA-Seq
revealed
that
could
enhance
efferocytosis
BMDMs
through
EPSIN1/low-density
lipoprotein
receptor-related
protein
1
(LRP1)
pathway
selectively
induce
apoptosis
(senolysis)
BMSCs.
mice,
we
period
prolonged
young
promoted
early
stage
osseointegration,
which
around
implant.
Collectively,
study
suggests
inhibition
accelerate
process
by
promoting
BMSCs
apoptosis.
implications
for
understanding
cellular
interactions
signaling
mechanisms
peri-implant
microenvironment
It
provide
clinical
significance
developing
new
therapies
quality
shorten
edentulous
patients.
CytoJournal,
Год журнала:
2025,
Номер
22, С. 11 - 11
Опубликована: Фев. 5, 2025
Objective:
Ubiquitin-specific
peptidase
14
(USP14)
may
be
a
target
for
stroke
treatment.
Our
study
aims
to
explore
the
molecular
mechanism
of
USP14
in
process.
Material
and
Methods:
A
cell
model
was
constructed
using
oxygen–glucose
deprivation/reoxygenation
(OGD/R)-induced
SK-N-SH
cells,
growth
assessed
counting
kit
8
assay,
EdU
flow
cytometry.
Proinflammatory
cytokine
levels
were
tested
through
an
enzyme-linked
immunosorbent
assay.
The
acyl-CoA
synthetase
long-chain
family
member
4
(ACSL4)
determined
Western
blot
quantitative
real-time
polymerase
chain
reaction,
whereas
interaction
ACS14
evaluated
by
co-immunoprecipitation
Results:
OGD/R-induced
injury
enhancing
ferroptosis
knockdown
inhibited
inflammation,
apoptosis,
ferroptosis.
Moreover,
enhanced
ACSL4
protein
expression
deubiquitination.
silencing
mitigated
neuron
injury,
upregulation
abolished
knockdown-mediated
inhibition
injury.
Conclusion:
can
enhance
stabilizing
expression.
Bone and Joint Research,
Год журнала:
2025,
Номер
14(5), С. 420 - 433
Опубликована: Май 9, 2025
Osteoporosis
a
is
metabolic
bone
disease
caused
by
an
imbalance
in
homeostasis,
which
regulated
osteoblasts
and
osteoclasts.
Protein
palmitoylation
modification
post-translational
that
affects
protein
function,
localization,
targeting
attaching
palmitoyl
groups
to
specific
amino
acid
residues
of
proteins.
Recent
studies
have
shown
involved
the
regulation
osteoclast
overproduction,
osteoblast
migration,
osteogenic
differentiation,
dysfunctional
autophagy,
endocrine
hormone
membrane
receptors
osteoporosis.
Exactly
what
extent
modifications
can
regulate
osteoporosis,
whether
inhibition
delay
key
question
needs
be
investigated
urgently.
In
this
review,
we
observed
act
mainly
through
two
target
cells
–
osteoclasts
targets
are
focused
on
plasma
proteins
or
cytosolic
cells,
tend
assume
role
receiving
extracellular
signals.
We
also
noted
different
transferases
acting
substrate
exert
conflicting
function.
concluded
osteocyte
osteoporosis
multidimensional,
diverse,
interconnected.
Perfecting
network
enhance
our
ability
utilize
resist
lay
foundation
for
treat
future.
Cite
article:
Bone
Joint
Res
2025;14(5):420–433.
Chemical Biology & Drug Design,
Год журнала:
2024,
Номер
103(2)
Опубликована: Фев. 1, 2024
Abstract
Icariin
has
been
shown
to
promote
osteogenic
differentiation
of
bone
marrow
mesenchymal
stem
cells
(BMSCs).
However,
the
underlying
molecular
mechanism
by
which
regulates
needs
be
further
revealed.
The
viability
BMSCs
was
assessed
cell
counting
kit
8
assay.
BMSC
ability
evaluated
detecting
alkaline
phosphatase
activity
and
performing
alizarin
red
S
staining.
protein
levels
differentiation‐related
markers,
sirtuin
1
(SIRT1),
ubiquitin‐specific
protease
47
(USP47),
Wnt/β‐catenin‐related
markers
were
determined
using
western
blot.
SIRT1
mRNA
level
measured
quantitative
real‐time
PCR.
regulation
USP47
on
confirmed
ubiquitination
detection
co‐immunoprecipitation
analysis.
could
differentiation.
expression
enhanced
Icariin,
its
knockdown
suppressed
Icariin‐induced
Moreover,
deubiquitinating
enzyme
stabilize
expression.
Besides,
overexpression
reversed
inhibiting
effect
differentiation,
also
restrained
Additionally,
Wnt/β‐catenin
pathway
upregulating
SIRT1.
facilitated
via
USP47/SIRT1/Wnt/β‐catenin
pathway.
Frontiers in Immunology,
Год журнала:
2024,
Номер
15
Опубликована: Сен. 16, 2024
Objective
To
identify
HBV-related
genes
(HRGs)
implicated
in
osteoporosis
(OP)
pathogenesis
and
develop
a
diagnostic
model
for
early
OP
detection
chronic
HBV
infection
(CBI)
patients.
Methods
Five
public
sequencing
datasets
were
collected
from
the
GEO
database.
Gene
differential
expression
LASSO
analyses
identified
linked
to
CBI.
Machine
learning
algorithms
(random
forests,
support
vector
machines,
gradient
boosting
machines)
further
filtered
these
genes.
The
best
was
chosen
based
on
accuracy
Kappa
values.
A
nomogram
HRGs
constructed
assessed
reliability.
patients
divided
into
two
clusters
using
non-negative
matrix
factorization.
Differential
gene
analysis,
Ontology,
KEGG
enrichment
explored
roles
of
progression,
ssGSEA
GSVA.
Differences
immune
cell
infiltration
between
correlation
cells
examined
Pearson
method.
Results
analysis
CBI
combined
dataset
822
776
differentially
expressed
genes,
respectively,
with
43
intersecting.
Following
various
machine
recursive
feature
elimination
algorithms,
16
identified.
emerged
as
predictive
values,
AUC
values
0.92,
0.83,
0.74,
0.7
training
set,
validation
GSE7429,
GSE7158,
respectively.
exhibited
0.91,
0.79,
0.68
Non-negative
factorization
clusters,
revealing
statistically
significant
differences
11
types
clusters.
Finally,
intersecting
obtained
three
Conclusion
This
study
successfully
developed
an
efficient
HRGs,
demonstrating
high
strong
performance
across
multiple
datasets.
research
not
only
offers
new
insights
complex
relationship
but
also
establishes
foundation
development
personalized
treatment
strategies
OP.
AJP Cell Physiology,
Год журнала:
2023,
Номер
326(2), С. C400 - C413
Опубликована: Дек. 18, 2023
Kidney
fibrosis
is
a
prominent
pathological
feature
of
hypertensive
kidney
diseases
(HKD).
Recent
studies
have
highlighted
the
role
ubiquitinating/deubiquitinating
protein
modification
in
pathophysiology.
Ovarian
tumor
domain-containing
6
A
(OTUD6A)
deubiquitinating
enzyme
involved
progression.
However,
its
pathophysiology
remains
elusive.
We
aimed
to
investigate
and
underlying
mechanism
OTUD6A
during
HKD.
The
results
revealed
higher
expression
tissues
nephropathy
patients
mice
with
chronic
angiotensin
II
(Ang
II)
administration
than
that
from
control
ones.
was
mainly
located
tubular
epithelial
cells.
Moreover,
deficiency
significantly
protected
against
Ang
II-induced
dysfunction
fibrosis.
Also,
knocking
down
suppressed
cultured
cells,
whereas
overexpression
enhanced
fibrogenic
responses.
Mechanistically,
bounded
signal
transducer
activator
transcription
3
(STAT3)
removed
K63-linked-ubiquitin
chains
promote
STAT3
phosphorylation
at
tyrosine
705
position
nuclear
translocation,
which
then
induced
profibrotic
gene
These
identified
as
direct
substrate
pivotal
injury,
indicating
potential
therapeutic
target
for
