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2017 ; 8
(10
): e3109
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gab.com Text
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Increased 15-lipoxygenase-1 expression in chondrocytes contributes to the
pathogenesis of osteoarthritis
#MMPMID29022900
Chen K
; Yan Y
; Li C
; Yuan J
; Wang F
; Huang P
; Qian N
; Qi J
; Zhou H
; Zhou Q
; Deng L
; He C
; Guo L
Cell Death Dis
2017[Oct]; 8
(10
): e3109
PMID29022900
show ga
15-Lipoxygenase-1 (15-LO-1) is involved in many pathological processes. The
purpose of this study was to determine the potential role of 15-LO-1 in
osteoarthritis (OA). The levels of 15-LO-1 expression were measured by western
blotting and quantitative real-time PCR in articular cartilage from the OA rat
models and OA patients. To further investigate the effects of 15-LO-1 on
chondrocyte functions, such as extracellular matrix (ECM) secretion, the release
of matrix-degrading enzymes, the production of reactive oxygen species (ROS),
cell proliferation and apoptosis, we decreased or increased 15-LO-1 expression in
chondrocytes by means of transfecting with siRNA targeting 15-LO-1 and plasmid
encoding 15-LO-1, respectively. The results showed that 15-LO-1 expression was
obviously increased in articular cartilage from OA rats and OA patients. It was
also found that many factor-related OA, such as mechanical loading, ROS, SNP and
inflammatory factor, significantly promoted 15-LO-1 expression and activity in
chondrocytes. Silencing 15-LO-1 was able to markedly alleviate mechanical
loading-induced cartilage ECM secretion, cartilage-degrading enzyme secretion and
ROS production. Overexpression of 15-LO-1 could inhibit chondrocyte proliferation
and induce chondrocyte apoptosis. In addition, reduction of 15-LO-1 in vivo
significantly alleviated OA. Taken together, these results indicate that 15-LO-1
has an important role in the disease progression of OA. Thus 15-LO-1 may be a
good target for developing drugs in the treatment of OA.