Sunaga Takafumi, Oh Namgil, Hosoya Kenji, Takagi Satoshi, Okumura Masahiro
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.
J Vet Med Sci. 2012 Jun;74(6):707-11. doi: 10.1292/jvms.11-0511. Epub 2011 Dec 28.
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.
聚多卡醇硫酸酯钠（PPS）具有类似肝素的结构，是从欧洲山毛榉木材中提纯得到的。PPS已被用于治疗人类患者的间质性膀胱炎。近年来，人们新认识到PPS可减轻骨关节炎的疼痛和炎症。PPS发挥其临床作用的分子生物学机制尚未完全明确。本研究的目的是探讨PPS在体外对软骨细胞炎症反应的作用机制。评估了PPS对白细胞介素（IL）-1β诱导的丝裂原活化蛋白激酶（MAPK）磷酸化的影响，如p38、细胞外信号调节激酶（ERK）和c-Jun氨基末端激酶（JNK），核因子κB（NF-κB）的核转位，以及培养的关节软骨细胞中基质金属蛋白酶（MMP）-3的产生。结果显示，在有PPS存在的情况下，IL-1β诱导的p38和ERK磷酸化确实受到抑制，而JNK磷酸化未受影响。在IL-1β刺激之前，PPS预处理可抑制NF-κB的核转位和MMP-3的产生。总之，强烈提示PPS治疗通过抑制某些MAPK（p38和ERK）的磷酸化以及随后培养的软骨细胞中NF-κB的核转位，预防IL-1β诱导的细胞内炎症反应。这些PPS特性可能有助于分解代谢性MMP-3合成的抑制作用。这些数据可能解释了PPS治疗的临床疗效，因为它可以抑制犬类骨关节炎的软骨分解代谢和相关临床症状。
