Advanced Science,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Dec. 24, 2024
Fibroblast
activation
protein
(FAP),
predominantly
expressed
in
activated
fibroblasts,
plays
a
key
role
inflammatory
bone
diseases,
but
its
periodontitis
remains
unclear.
Accordingly,
this
study
identified
positive
association
between
FAP
levels
and
susceptibility
using
Mendelian
randomization
analysis.
Human
mouse
tissues
show
elevated
reduced
osteolectin
(OLN),
an
endogenous
inhibitor,
indicating
FAP/OLN
imbalance.
Single-cell
RNA
sequencing
revealed
gingival
fibroblasts
(GFs)
as
the
primary
OLN
source,
with
periodontitis-associated
GFs
showing
increased
reactive
oxygen
species,
cellular
senescence,
mTOR
pathway
activation.
Rapamycin
treatment
restored
balance
GFs.
Recombinant
pro-inflammatory
cytokine
secretion
osteoclast
differentiation
macrophages,
exacerbating
periodontal
damage,
whereas
inhibition
macrophage
inflammation,
collagen
degradation,
resorption
experimental
periodontitis.
Therefore,
senescent
drive
imbalance
through
activation,
contributing
to
progression.
Consequently,
targeting
may
offer
promising
therapeutic
strategy
for
Current Issues in Molecular Biology,
Journal Year:
2025,
Volume and Issue:
47(1), P. 38 - 38
Published: Jan. 9, 2025
Rheumatoid
arthritis
(RA)
is
an
autoimmune
disorder
that
leads
to
severe
cartilage
deterioration
and
synovial
impairment
in
the
joints.
Previous
studies
have
indicated
aberrant
activation
of
NLRP3
inflammasome
macrophages
plays
a
significant
role
pathogenesis
RA
has
been
regarded
as
therapeutic
target
for
disease.
In
this
study,
we
synthesized
novel
canthin-6-one
alkaloid,
namely
methyl
canthin-6-one-2-carboxylate
(Cant),
assessed
its
effects
on
macrophages.
Our
data
reveal
exposure
Cant
significantly
suppressed
transcription
secretion
multiple
pro-inflammatory
mediators,
including
IL-1β,
IL-6,
IL-18,
TNF-α,
NO,
COX2,
dose-dependent
manner.
These
alterations
were
associated
with
changes
various
signaling
pathways,
NF-kB,
MAPK,
PI3K-AKT
pathways.
Notably,
pretreatment
reduced
LPS/ATP-induced
inflammasome,
evidenced
by
decline
cleaved
forms
IL-1β
caspase-1
cell
culture
supernatants
BMDMs.
Regarding
mechanisms,
our
show
could
enhance
expression
Nrf2
macrophages,
which
play
inhibitory
ROS
production.
Collectively,
demonstrate
might
suppress
upregulating
production
Nrf2,
suggesting
serve
candidate
further
development
anti-RA
drugs.
Journal of Inflammation Research,
Journal Year:
2025,
Volume and Issue:
Volume 18, P. 2743 - 2765
Published: Feb. 1, 2025
The
crosstalk
between
H-type
endothelial
cells
(ECs)
and
macrophages
is
critical
for
maintaining
angiogenesis
osteogenesis
in
bone
homeostasis.
As
core
components
of
type
H
vessels,
ECs
respond
to
various
pro-angiogenic
signals,
forming
specialized
vascular
structures
characterized
by
high
expression
platelet-endothelial
cell
adhesion
molecule-1
(CD31)
mucin
(EMCN),
thereby
facilitating
angiogenesis-osteogenesis
coupling
during
formation.
Macrophages,
as
key
immune
the
perivascular
region,
are
primarily
classified
into
classically
activated
pro-inflammatory
M1
phenotype
selectively
anti-inflammatory
M2
phenotype,
performing
dual
functions
regulating
local
tissue
homeostasis
innate
immunity.
In
recent
years,
complex
vessel
has
garnered
significant
interest
context
bone-related
diseases.
Orderly
regulation
immunity
provides
a
new
direction
preventing
metabolic
disorders
such
osteoporosis
osteoarthritis.
However,
their
interactions
remain
insufficiently
understood,
with
limited
clinical
data
available.
This
review
comprehensively
examines
intricate
diverse
phenotypes,
Insights
signaling
pathways
that
regulate
crosstalk,
focusing
on
roles
osteogenesis.
Furthermore,
discusses
interventions
targeting
this
challenges
remain.
These
insights
may
offer
perspectives
provide
theoretical
foundation
developing
novel
therapeutic
strategies.
Journal of Orthopaedic Surgery and Research,
Journal Year:
2025,
Volume and Issue:
20(1)
Published: March 18, 2025
The
objective
of
this
study
was
to
identify
potential
genes
implicated
in
the
"peri-collapse"
synovium
osteonecrosis
femoral
head
through
coding
gene
sequencing
and
further
clarify
their
specific
mechanisms
via
vitro
experiments.
Steroid-induced
(SIONFH)
(n
=
3),
neck
fracture
(FNF)
hip
osteoarthritis
(HOA)
3)
Synovial
tissue
joint
collected
total
arthroplasty.
A
cellular
model
SIONFH
constructed
from
rat
synovial
fibroblasts
by
lipopolysaccharide
intervention.
Lentiviral
technology
used
construct
a
for
fibroblast
knockout
Irf7
gene.
HE
compare
characteristics
damage,
immunofluorescence
immunohistochemistry
were
expression
levels
VIM,
IRF7,
IFNα.
PCR,
WB,
IF
examine
knockdown
efficiency,
chondrocyte
proliferation
(Col2a1,
Aggrecan,
Sox9),
cartilage
matrix
degradation
(Mmp13),
apoptosis
(Bcl2,
Bax,
Caspase3)
under
co-culture
conditions.
Crystalline
violet
staining
observe
migration
rate
fibroblasts,
flow
cytometry
detect
level
chondrocytes
Transcriptome
ultimately
screened
six
differential
genes,
HOOK1,
RNPC3,
KCNA3,
CD48,
SAMD9.
Compared
FNF
HOA,
inflammatory
cell
recruitment
hyperplasia
more
pronounced
SIONFH.
IHC
confirmed
high
IRF7
IFNα
PCR
WB
results
suggested
that
highly
expressed
Irf7,
Hook1,
Rnpc3,
Kcna3,
Cd48,
Samd9,
Il-6,
Tnfα
after
intervention,
Il-6
significantly
reduced
(P
<
0.001).
In
system,
intervened
with
promoted
apoptosis,
degradation,
while
inhibiting
proliferation,
result
reversed
fibroblasts.
This
supported
results.
SAMD9
as
affecting
progression
collapse.
mediates
response
affects
collapse
process
influencing
apoptosis.
Thus,
intervention
holds
promise
one
key
targets
reversing
