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2016 ; 7
(2
): e2099
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AIMP1 downregulation restores chondrogenic characteristics of
dedifferentiated/degenerated chondrocytes by enhancing TGF-? signal
#MMPMID26890138
Ahn J
; Kumar H
; Cha BH
; Park S
; Arai Y
; Han I
; Park SG
; Lee SH
Cell Death Dis
2016[Feb]; 7
(2
): e2099
PMID26890138
show ga
Dedifferentiation and degeneration of chondrocytes critically influences the
efficiency of cartilage repair. One of the causes is the defect of transforming
growth factor (TGF)-? signaling that promotes chondrogenic differentiation and
degeneration. In the present study, we found that aminoacyl-tRNA
synthetase-interacting multifunctional protein 1 (AIMP1) negatively regulates
TGF-? signaling via interactions with Smad2 and Smad3 in immunoprecipitation
assay and luciferase assay. In addition, we observed that the AIMP1 expression
level was significantly increased in osteoarthritis (OA) patient-derived
degenerated chondrocytes compared with healthy control. So, we hypothesized that
downregulation of AIMP1 using small-interfering RNA (siRNA) technology in
dedifferentiated (collected at passage #6) and degenerated (obtained from
OA-affected areas) chondrocytes could lead to recover TGF-? signaling in both
chondrocytes. Indeed, AIMP1 downregulation restored TGF-? signaling by promoting
phosphorylation of Smad2 and Smad3, which shows redifferentiated characteristics
in both dedifferentiated and degenerated chondrocytes. Additionally, implantation
analyses using in vivo mouse model clearly showed that AIMP1 downregulation
resulted in the increased chondrogenic potential as well as the enhanced
cartilage tissue formation in both dedifferentiated and degenerated chondrocytes.
Histological analyses clarified that AIMP1 downregulation increased expression
levels of collagen type II (Col II) and aggrecan, but not Col I expression. Taken
together, these data indicate that AIMP1 downregulation using siRNA is a novel
tool to restore TGF-? signaling and thereby increases the chondrogenic potential
of dedifferentiated/degenerated chondrocytes, which could be further developed as
a therapeutic siRNA to treat OA.
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