Prostaglandin E2 and its cognate EP receptors control human adult articular cartilage homeostasis and are linked to the pathophysiology of osteoarthritis.
Prostaglandin E2 and its cognate EP receptors control human adult articular cartilage homeostasis and are linked to the pathophysiology of osteoarthritis.
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DOI：
10.1002/art.24258
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发表时间：
2009-02
影响因子：
--
通讯作者：
Im, Hee-Jeong
中科院分区：
文献类型：
--
作者：
Li, Xin;Ellman, Michael;Muddasani, Prasuna;Wang, James H. -C.;Cs-Szabo, Gabriella;van Wijnen, Andre J.;Im, Hee-Jeong
通过表征 PGE2 及其独特受体在人类成人关节软骨细胞中的分解代谢作用，阐明前列腺素 E2 (PGE2) 与骨关节炎之间的病理生理联系。将成人关节软骨细胞培养在单层或藻酸盐珠中，有或没有PGE2和/或EP受体激动剂、拮抗剂和细胞因子。在藻酸盐珠中测量细胞存活、增殖以及总蛋白聚糖合成和积累。使用单层细胞培养模型分别通过实时 PCR 和蛋白质印迹评估软骨细胞相关基因表达和 PI3k/Akt 信号传导。通过 EP2 受体用 PGE2 刺激人关节软骨细胞 (i) 抑制蛋白聚糖的积累和合成，(ii) 抑制聚集蛋白聚糖基因表达，(iii) 不会明显影响基质降解酶的表达； (iv) 降低胶原蛋白 II:I 的比例。与踝关节软骨相比，EP2 和 EP4 受体在膝关节软骨中的表达水平较高，且表达水平呈等级依赖性。 PGE2 滴定与 IL-1 结合可协同加速疼痛相关分子的表达，例如诱导型一氧化氮合酶 (iNOS) 和 IL-6。最后，用外源性 PGE2 或 EP2 激动剂刺激可抑制胰岛素样生长因子 (IGF-1) 诱导的 Akt 激活。 PGE2在体外对成人关节软骨发挥抗合成代谢作用，EP2/4受体拮抗剂可能是治疗骨关节炎的有效治疗剂。
To elucidate the pathophysiologic links between prostaglandin E2 (PGE2) and osteoarthritis by characterizing the catabolic effects of PGE2 and its unique receptors in human adult articular chondrocytes. Human adult articular chondrocytes were cultured in monolayer or alginate beads with and without PGE2 and/or agonist, antagonist of EP receptors and cytokines. Cell survival, proliferation, and total proteoglycan synthesis and accumulation were measured in alginate beads. Chondrocyte-related gene expression and PI3k/Akt signaling were assessed by real-time PCR and western blotting, respectively, using a monolayer cell culture model. Stimulation of human articular chondrocytes with PGE2 through the EP2 receptor (i) suppresses proteoglycan accumulation and synthesis, (ii) suppresses aggrecan gene expression, (iii) does not appreciably affect expression of matrix-degrading enzymes; and (iv) decreases the collagen II:I ratio. EP2 and EP4 receptors are expressed at higher levels in knee compared to ankle cartilage, and in a grade-dependent fashion. PGE2 titration combined with IL-1 synergistically accelerates expression of pain-associated molecules such as inducible nitric oxide synthase (iNOS) and IL-6. Finally, stimulation with exogenous PGE2 or an EP2 agonist inhibits activation of Akt that is induced by insulin-like growth factor (IGF-1). PGE2 exerts an anti-anabolic effect on human adult articular cartilage in vitro, and EP2/4 receptor antagonists may represent effective therapeutic agents for the treatment of osteoarthritis.
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影响因子：
4
作者：
Iannone, F;Lapadula, G
通讯作者：
Lapadula, G
影响因子：
--
作者：
LIPPIELLO, L;YAMAMOTO, K;MANKIN, HJ
通讯作者：
MANKIN, HJ
影响因子：
--
作者：
Kim, Hyun Ah;Cho, Mi-La;Kim, Ho-Youn
通讯作者：
Kim, Ho-Youn
影响因子：
6.2
作者：
Aoyama, T;Liang, BJ;Toguchida, J
通讯作者：
Toguchida, J
影响因子：
7
作者：
Fushimi, K;Nakashima, S;Shimizu, K
通讯作者：
Shimizu, K