Publication: Suppression of cartilage degeneration by intra-articular injection of heparan sulfate 6-O endosulfatase in a mouse osteoarthritis model
Authors
Otsuki, Shuhei ; Murakami, Tomohiko ; Okamoto, Yoshinori ; Hoshiyama, Yoshiaki ; Oda, Shuhei ; Neo, Masashi
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Publisher
Universidad de Murcia. Departamento de Biología Celular e Histología
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DOI
DOI: 10.14670/HH-11-838
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info:eu-repo/semantics/article
Description
Abstract
We previously reported that heparan sulfate
6-O endosulfatases (Sulfs) were expressed in articular
cartilage, and that the Sulf-1 knockout mouse developed
severe knee osteoarthritis. In this study, we hypothesised
that intra-articular injection of Sulf-1 would prevent
cartilage degeneration. After confirming that 1 mg/ml
Sulf-1 did not induce ATDC5 cell death in vitro, gene
expression of type II collagen and matrix metalloproteinase (MMP)-13 in the presence of Sulf-1 (1-100
ng/ml) were determined by quantitative real-time
polymerase chain reaction. Sulf-1 was also injected
intra-articularly into mice following surgical
destabilisation of the medial meniscus to produce a
model of osteoarthritis, and cartilage degeneration was
evaluated by safranin O and MMP-13 staining. We also
investigated fibroblast growth factor 2 (FGF2)/
extracellular signal-regulated kinase (Erk) cell signalling
by western blotting. Exposure to Sulf-1 in vitro
increased type II collagen expression and decreased
MMP-13 expression in a concentration-dependent
manner. Sulf-1 injection into the mouse osteoarthritic
knee significantly suppressed glycosaminoglycan loss
and MMP-13 expression. Erk1/2 signalling pathway
activation was significantly reduced by Sulf-1 and
FGF2. These findings indicate that Sulf-1 prevents
cartilage degeneration by suppressing MMP-13 via an
effect on FGF2/Erk1/2 signalling.
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