Inhibitory effects of pentosan polysulfate sodium on MAP-kinase pathway and NF-κB nuclear translocation in canine chondrocytes in vitro.
Pentosan polysulfate sodium (PPS) has a heparin-like structure and is purificated from the plant of European beech wood. PPS has been used for the treatment of interstitial cystitis for human patients. Recent years, it was newly recognised that PPS reduce pain and inflammation of OA. The molecular biological mechanism of PPS to express its clinical effects is not fully understood. The purpose of the present study is to investigate a mechanism of action of PPS on inflammatory reaction of chondrocytes in vitro. It was evaluated that effects of PPS on interleukin (IL)-1β-induced phosphorylation of mitogen-actiated protein kinases (MAPKs), such as p38, extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK), nuclear translocation of nuclear factor-kappa B (NF-κB), and matrix metalloproteinase (MMP)-3 production in cultured articular chondrocytes. As a result, in the presence of PPS existence, IL-1β-induced phosphorylation of p38 and ERK were certainly inhibited, while JNK phosphorylation was not affected. Nuclear translocation of NF-κB and MMP-3 production were suppressed by PPS pretreatment prior to IL-1β stimulation. In conclusion, it is strongly suggested that PPS treatment prevents inflammatory intracellular responses induced by IL-1 β through inhibition of phosphorylation of certain MAPKs, p38 and ERK and then nuclear translocation of NF-κB in cultured chondrocytes. These PPS properties may contribute to suppressive consequence of catabolic MMP-3 synthesis. These data might translate the clinical efficacy as PPS treatment could inhibit the cartilage catabolism and related clinical symptoms of OA in dogs.
Laboratory of Veterinary Surgery, Department of Veterinary Clinical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Kita 18 Nishi 9, Kita-ku, Sapporo, Hokkaido 060-0818, Japan.
Takafumi
T
Sunaga
Namgil
N
Oh
Kenji
K
Hosoya
Satoshi
S
Takagi
Masahiro
M
Okumura
D021581:Active Transport, Cell Nucleus / Q000187:drug effects / Q000502:physiology; D000818:Animals; D015153:Blotting, Western / Q000662:veterinary; D002467:Cell Nucleus / Q000378:metabolism*; D019902:Chondrocytes / Q000201:enzymology* / Q000502:physiology; D017931:DNA Primers / Q000235:genetics; D004285:Dogs; D066298:In Vitro Techniques; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000502:physiology; D019278:Matrix Metalloproteinase 3 / Q000096:biosynthesis; D016328:NF-kappa B / Q000378:metabolism*; D010426:Pentosan Sulfuric Polyester / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D060888:Real-Time Polymerase Chain Reaction / Q000662:veterinary; D018709:Statistics, Nonparametric
D017931:DNA Primers; D016328:NF-kappa B; D010426:Pentosan Sulfuric Polyester; D019278:Matrix Metalloproteinase 3