Constructing a cross-tissue human knee single-cell atlas identified osteoarthritis reduces regenerative tissue stem cells while increasing inflammatory pain macrophages
Research Square (Research Square),
Journal Year:
2025,
Volume and Issue:
unknown
Published: May 5, 2025
Abstract
Osteoarthritis
(OA)
affects
the
entire
knee
joint;
however,
cross-tissue
molecular
mechanisms
are
poorly
understood
due
to
a
lack
of
comprehensive,
integrated
analysis.
We
constructed
first
comprehensive
single-cell
RNA
sequencing
OA
atlas
from
articular
cartilage,
meniscus,
synovium,
and
subchondral
bone
which
showed
active
communication
between
them.
Healthy
synovium
meniscus
contain
largest
populations
tissue
stem
cells
(TSCs)
immune
that
altered
in
OA.
The
regenerative
TSCs
expressing
SDF1,
SOX9,
CD146,
PDGFRB,
CD105
decrease
during
OA,
whereas
osteogenic
differentiation-related
factor
NT5E
(CD73)
increased.
In
balance
shifts
state
with
an
increased
number
TSCs.
also
report
level
quadruple-positive
inflammatory
(IL1B-IL6-NOS2-TNF)
pain
marker
(P2RX7)
specific
macrophages
Fibroblasts
enriched
OA-synovium
may
contribute
fibrosis.
Importantly,
cartilage
contains
unique
MMP13-producing
detrimental
chondrocytes
along
RUNX2-producing
worsen
pathophysiology.
This
provides
novel
avenue
for
potential
therapeutic
applications
human
other
musculoskeletal
diseases
injuries,
targeting
intervene
OA-specific
cellular
alterations.
Language: Английский
New developments in osteoporosis, osteoarthritis and soft tissue repair
Journal of Orthopaedic Translation,
Journal Year:
2024,
Volume and Issue:
49, P. A1 - A2
Published: Nov. 1, 2024
Language: Английский