Journal of Experimental & Clinical Cancer Research,
Год журнала:
2024,
Номер
43(1)
Опубликована: Фев. 12, 2024
Nasopharyngeal
carcinoma
(NPC)
poses
a
significant
health
burden
in
specific
regions
of
Asia,
and
some
NPC
patients
have
bone
metastases
at
the
time
initial
diagnosis.
Bone
metastasis
can
cause
pathologic
fractures
pain,
reducing
patients'
quality
life,
is
associated
with
worse
survival.
This
study
aims
to
unravel
complex
role
insulin-like
growth
factor
1
receptor
(IGF-1R)
metastasis,
offering
insights
into
potential
therapeutic
targets.
We
assessed
IGF-1R
expression
cells
explored
its
correlation
metastasis.
Experiments
investigated
impact
osteoclast-secreted
IGF-1
on
IGF-1R/AKT/S6
pathway
promoting
cell
proliferation
within
marrow.
Additionally,
reciprocal
influence
tumor-secreted
Granulocyte-macrophage
colony-stimulating
(GM-CSF)
osteoclast
differentiation
resorption
was
examined.
The
effects
neutralizing
antibody,
inhibitor
(NVP-AEW541)
mTORC
(rapamycin)
nasopharyngeal
were
also
animal
experiments.
Elevated
correlated
an
increased
tendency
for
IGF-1,
secreted
by
osteoclasts,
activated
pathway,
Tumor-secreted
GM-CSF
further
stimulated
differentiation,
exacerbating
resorption.
NVP-AEW541
rapamycin
respectively
effective
slowing
down
rate
destruction.
intricate
interplay
among
IGF-1R,
highlights
targets
precise
control
providing
valuable
developing
targeted
interventions.
Abstract
Following
the
discovery
of
bone
as
an
endocrine
organ
with
systemic
influence,
bone-brain
interaction
has
emerged
a
research
hotspot,
unveiling
complex
bidirectional
communication
between
and
brain.
Studies
indicate
that
brain
can
influence
each
other’s
homeostasis
via
multiple
pathways,
yet
there
is
dearth
systematic
reviews
in
this
area.
This
review
comprehensively
examines
interactions
across
three
key
areas:
bone-derived
factors
on
function,
effects
brain-related
diseases
or
injuries
(BRDI)
health,
concept
skeletal
interoception.
Additionally,
discusses
innovative
approaches
biomaterial
design
inspired
by
mechanisms,
aiming
to
facilitate
through
materiobiological
aid
treatment
neurodegenerative
bone-related
diseases.
Notably,
integration
artificial
intelligence
(AI)
highlighted,
showcasing
AI’s
role
expediting
formulation
effective
targeted
strategies.
In
conclusion,
offers
vital
insights
into
mechanisms
suggests
advanced
harness
these
clinical
practice.
These
offer
promising
avenues
for
preventing
treating
impacting
skeleton
brain,
underscoring
potential
interdisciplinary
enhancing
human
health.
Bone
undergoes
constant
remodeling
by
osteoclast
bone
resorption
coupled
with
osteoblast
formation
at
the
surface.
A
third
major
cell
type
in
is
osteocytes,
which
are
embedded
matrix,
well-connected
to
lacunar
network,
and
believed
act
as
mechanical
sensors.
Here,
it
reported
that
sympathetic
innervation
directly
regulates
osteocyte-mediated
inside
cortical
bone.
It
found
activity
elevated
different
mouse
models
of
loss,
including
lactation,
ovariectomy,
glucocorticoid
treatment.
Further,
during
lactation
outflow
induces
netrin-1
expression
osteocytes
further
promote
nerve
sprouting
endosteum
a
feed-forward
loop.
Depletion
tyrosine
hydroxylase-positive
(TH+
)
nerves
ameliorated
perilacunar
lactating
mice.
Moreover,
norepinephrine
activates
β-adrenergic
receptor
2
(Adrb2)
signaling
secretion
extracellular
vesicles
(EVs)
containing
bone-degrading
enzymes
for
inhibit
differentiation.
Importantly,
osteocyte-specific
deletion
Adrb2
or
treatment
β-blocker
results
lower
Together,
these
findings
show
nervous
system
promotes
osteocyte-driven
loss
likely
an
adaptive
response
increased
energy
mineral
demands
nursing
mother.
Abstract
Recent
studies
have
determined
that
the
nervous
system
can
sense
and
respond
to
signals
from
skeletal
tissue,
a
process
known
as
interoception,
which
is
crucial
for
maintaining
bone
homeostasis.
The
hypothalamus,
located
in
central
(CNS),
plays
key
role
processing
interoceptive
regulating
homeostasis
through
autonomic
system,
neuropeptide
release,
neuroendocrine
mechanisms.
These
mechanisms
control
differentiation
of
mesenchymal
stem
cells
into
osteoblasts
(OBs),
activation
osteoclasts
(OCs),
functional
activities
cells.
Sensory
nerves
extensively
innervate
tissues,
facilitating
transmission
CNS.
This
review
provides
comprehensive
overview
current
research
on
generation
coordination
by
CNS
maintain
their
potential
pathological
conditions.
findings
expand
our
understanding
intersystem
communication
biology
may
implications
developing
novel
therapeutic
strategies
diseases.
Abstract
Microgravity
is
the
primary
factor
that
affects
human
physiology
in
spaceflight,
particularly
bone
loss
and
disturbances
of
central
nervous
system.
However,
little
known
about
cellular
molecular
mechanisms
these
effects.
Here,
it
reported
mice
hindlimb
unloading
stimulates
expression
neuropeptide
Y
(NPY)
tyrosine
hydroxylase
(TH)
hypothalamus,
resulting
altered
fat
metabolism.
Enhanced
TH
NPY
hypothalamus
occurs
downstream
a
reduced
prostaglandin
E2
(PGE2)‐mediated
ascending
interoceptive
signaling
skeletal
interoception.
Sympathetic
antagonist
propranolol
or
deletion
Adrb2
osteocytes
rescue
model.
Moreover,
depletion
+
sympathetic
nerves
inhibition
norepinephrine
release
ameliorated
resorption.
Stereotactic
hypothalamic
neurons
reduces
food
intake
with
energy
expenditure
limited
effect
on
bone,
indicating
neuroendocrine
facilitation
formation
by
activity.
These
findings
suggest
PGE2‐mediated
response
to
microgravity
has
impacts
systems
are
reciprocally
regulated.
Abstract
Accumulating
research
has
shed
light
on
the
significance
of
skeletal
interoception,
in
maintaining
physiological
and
metabolic
homeostasis
related
to
bone
health.
This
review
provides
a
comprehensive
analysis
how
interoception
influences
homeostasis,
delving
into
complex
interplay
between
nervous
system
system.
One
key
focus
is
role
various
factors
such
as
prostaglandin
E2
(PGE2)
health
via
interoception.
It
explores
nerves
innervating
tissue
communicate
with
central
regulate
remodeling,
process
critical
for
strength
integrity.
Additionally,
highlights
advancements
biomaterials
designed
utilize
enhancing
regeneration
treatment
disorders.
These
biomaterials,
tailored
interact
body’s
interoceptive
pathways,
are
positioned
at
forefront
innovative
treatments
conditions
like
osteoporosis
fractures.
They
represent
convergence
bioengineering,
neuroscience,
orthopedics,
aiming
create
more
efficient
targeted
therapies
bone-related
In
conclusion,
underscores
importance
regulation
its
potential
developing
effective
regeneration.
emphasizes
need
further
fully
understand
mechanisms
harness
therapeutic
fully.
Aging Clinical and Experimental Research,
Год журнала:
2025,
Номер
37(1)
Опубликована: Янв. 21, 2025
Abstract
Objective
Osteoarthritis
(OA)
represents
a
condition
under
the
influence
of
central
nervous
system
(CNS)
regulatory
mechanisms.
This
investigation
aims
to
examine
causal
association
between
viral
infections
(VICNS)
and
inflammatory
diseases
(IDCNS)
knee
osteoarthritis
(KOA)
at
genetic
level.
Methods
In
this
investigation,
VICNS
IDCNS
were
considered
as
primary
exposure
variables,
while
KOA
served
outcome.
Employing
two-sample
mendelian
randomization
(MR)
approach,
we
conducted
an
analysis
utilizing
summary
data
derived
from
genome-wide
studies
(GWAS).
The
GWAS
pertaining
procured
Finnish
consortium,
whereas
IEU
OpenGWAS
database
furnished
requisite
for
KOA.
To
ensure
robustness
our
assessment,
comprehensive
array
sensitivity
analyses
was
undertaken,
encompassing
evaluations
heterogeneity,
horizontal
pleiotropy,
outlier
identification,
leave-one-out
analyses,
assessment
normal
distribution.
Results
results
MR
revealed
suggestive
positive
relationship
(
P
=
0.012,
odds
ratio
[OR]
with
95%
confidence
interval
[CI]
1.033
[1.007–1.059]).
Conversely,
did
not
indicate
any
evidence
causation
0.575,
OR
CI
0.986
[0.940–1.035]).
Importantly,
outcome
variables
demonstrate
indications
or
outliers.
Furthermore,
remained
robust
against
individual
single
nucleotide
polymorphisms
(SNPs)
exhibited
adherence
Conclusion
result
study
has
elucidated
link
However,
no
such
observed
These
findings
substantiate
underpinnings
supporting
CNS
OA.
Journal of Orthopaedic Surgery and Research,
Год журнала:
2025,
Номер
20(1)
Опубликована: Фев. 12, 2025
Despite
being
a
leading
cause
of
chronic
pain
and
disability,
the
underlying
mechanisms
intervertebral
disc
(IVD)
degeneration
(IVDD)
remain
unclear.
Emerging
evidence
suggests
that
mechanosensation
(the
ability
skeletal
system
to
perceive
mechanical
biochemical
signals)
mediated
by
abnormal
loading
plays
critical
role
in
regulation
IVD
health.
This
review
examines
complex
interactions
amongIVDs,
intraosseous
sensory
mechanisms,
central
nervous
(CNS),
with
particular
focus
on
roles
pathways
such
as
PGE2/EP4,
Wnt/β-catenin,
NF-κB.
elucidates
manner
which
stress
aberrant
signaling
disrupt
homeostasis
nucleus
pulposus
(NP),
cartilaginous
endplate
(CEP)
annulus
fibrosus
(AF),
thereby
driving
exacerbating
pain.
Furthermore,
targeted
therapeutic
strategies,
including
modulation
interoception
dynamic
loading,
present
novel
avenues
for
reversing
IVDD
progression.
By
integrating
biology
spinal
pathology,
this
work
offers
perspective
pathogenesis
identifies
promising
strategies
clinical
intervention.
These
findings
highlight
potential
targeting
mitigate
associated
pain,
paving
way
innovative,
mechanism-driven
therapies.
