Dysregulated Mechanotransduction via CCNB2 Underlies Fibroblast Hypoplasia in Developmental Dysplasia of the Hip
Abstract
Purpose:
Developmental
dysplasia
of
the
hip
(DDH)
involves
structural
and
functional
impairments
in
joint
capsule;
however,
molecular
mechanisms
underlying
these
changes
remain
unclear.
This
study
aimed
to
identify
biomarkers
associated
with
fibroblast
mechanical
signaling
capsule
patients
DDH
explore
their
potential
roles
disease
pathogenesis.
Methods:
Joint
tissues
were
collected
from
age‐
sex‐matched
healthy
controls.
RNA
sequencing
(RNA-seq)
identified
differentially
expressed
cell-cell
communication-related
genes
(DE-CMRGs).
Five
bioinformatics
algorithms
(MCC,
MNC,
Degree,
Closeness,
Eccentricity)
applied
key
DE-CMRGs
correlated
function.
Biomarker
validation
was
performed
using
reverse
transcription
quantitative
PCR
(RT-qPCR),
Western
blot,
immunohistochemistry
(IHC),
hematoxylin-eosin
(HE)
staining.
Additionally,
immune
infiltration
analysis
regulatory
network
construction
(TF-mRNA
lncRNA-miRNA-mRNA
ceRNA
networks)
conducted
elucidate
mechanisms.
Results:
Transcriptomic
revealed
155
DE-CMRGs,
which
five
(KIF20A,
BUB1,
CCNB2,
AURKB,
BUB1B)
identified.
These
significantly
downregulated
samples.
Functional
enrichment
analyses
highlighted
involvement
pathways
related
muscle
contraction,
extracellular
matrix
interactions,
cell
cycle
regulation,
responses.
Immune
showed
correlations
between
specific
populations,
particularly
memory-activated
CD4
T
cells,
macrophages,
neutrophils,
dendritic
monocytes.
Experimental
confirmed
that
CCNB2
at
both
mRNA
protein
levels
compared
Histopathological
examinations
reduced
density
altered
cellular
architecture
decreased
expression.
Conclusion:
This
identifies
validates
novel
biomarkers,
communication
fibroblasts
DDH.
together
networks,
offer
new
insights
into
pathogenesis
highlight
targets
for
early
diagnosis
therapeutic
intervention.
Research Square (Research Square), Год журнала: 2025, Номер unknown
Опубликована: Май 7, 2025
Язык: Английский