Frontiers in Pharmacology,
Год журнала:
2024,
Номер
15
Опубликована: Авг. 29, 2024
Osteoarthritis
(OA)
is
the
most
prevalent
cartilage
degenerative
and
low-grade
inflammatory
disease
of
whole
joint.
However,
there
are
currently
no
FDA-approved
drugs
or
global
regulatory
agency-approved
treatments
OA
modification.
Therefore,
it’s
essential
to
explore
novel
effective
therapeutic
strategies
for
OA.
In
our
study,
we
investigated
effects
AFK-PD,
a
pyridone
agent,
on
development
induced
by
destabilization
medial
meniscus
(DMM)
in
vivo
,
its
impact
function
chondrocytes
treated
with
IL-1β
vitro
.
Our
results
demonstrated
AFK-PD
alleviated
progression
through
inhibiting
degeneration,
articular
inflammation
osteophyte
formation.
Notably,
inhibited
chondrocyte
synovial
macrophage
M1
polarization,
leading
attenuation
inflammation.
Additionally,
promoted
anabolism
while
mitigating
catabolism
apoptosis,
effectively
degeneration.
Mechanistically,
suppressed
expression
key
signaling
molecules
involved
MAPK
pathway,
such
as
p-ERK1/2
p-JNK,
well
NF-κB
molecule
p-p65,
IL-1β-induced
chondrocytes.
These
findings
suggest
ameliorates
protecting
functions
macrophages.
Overall,
study
highlights
promising
candidate
treatment
Background:
Knee
joint
osteoarthritis,
a
widespread
disabling
disease
with
no
known
cause
continues
to
produce
considerable
bouts
of
intractable
pain
and
disability
as
result
multiple
associated
health
problems
despite
years
research.
Aim:
This
paper
examines
if
there
is
sufficient
reason
believe
one
or
more
neural
based
abnormalities
in
the
knee
network
may
be
involved
implicated
inducing
perpetuating
at
least
some
forms
but
often
unrecognized
thus
untreated
ignored.
Methods:
Peer
reviewed
data
retrieved
from
several
sources
were
examined
highlight
discuss
structural
functional
nature
nerves
their
ramifications
various
tissues,
spinal
cord
central
nervous
system
motor
control
pathways.
Results:
nerve
pathways
that
are
damaged
functioning
abnormally
can
affect
normal
biomechanics,
plus
stability
thereby
influence
onset
perpetuation
pathology
exaggerated
activation
fibers
cognitions.
Conclusion:
To
improve
effectiveness
strategies
designed
avert
osteoarthritis
disability,
attention
its
possible
ongoing
neuropathology
well
declines
protective,
perceptual
mechanisms
older
vulnerable
adults
indicated.
Frontiers in Pharmacology,
Год журнала:
2024,
Номер
15
Опубликована: Авг. 29, 2024
Osteoarthritis
(OA)
is
the
most
prevalent
cartilage
degenerative
and
low-grade
inflammatory
disease
of
whole
joint.
However,
there
are
currently
no
FDA-approved
drugs
or
global
regulatory
agency-approved
treatments
OA
modification.
Therefore,
it’s
essential
to
explore
novel
effective
therapeutic
strategies
for
OA.
In
our
study,
we
investigated
effects
AFK-PD,
a
pyridone
agent,
on
development
induced
by
destabilization
medial
meniscus
(DMM)
in
vivo
,
its
impact
function
chondrocytes
treated
with
IL-1β
vitro
.
Our
results
demonstrated
AFK-PD
alleviated
progression
through
inhibiting
degeneration,
articular
inflammation
osteophyte
formation.
Notably,
inhibited
chondrocyte
synovial
macrophage
M1
polarization,
leading
attenuation
inflammation.
Additionally,
promoted
anabolism
while
mitigating
catabolism
apoptosis,
effectively
degeneration.
Mechanistically,
suppressed
expression
key
signaling
molecules
involved
MAPK
pathway,
such
as
p-ERK1/2
p-JNK,
well
NF-κB
molecule
p-p65,
IL-1β-induced
chondrocytes.
These
findings
suggest
ameliorates
protecting
functions
macrophages.
Overall,
study
highlights
promising
candidate
treatment
