Prostaglandin F2α receptor (FP) signaling regulates Bmp signaling and promotes chondrocyte differentiation.
Prostaglandin F2α receptor (FP) signaling regulates Bmp signaling and promotes chondrocyte differentiation.
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DOI：
10.1016/j.bbamcr.2014.12.003
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发表时间：
2015-02
影响因子：
5.1
通讯作者：
Shim, Minsub
中科院分区：
文献类型：
--
作者：
Kim, Joohwee;Shim, Minsub
前列腺素是一组参与各种生理过程的脂质信号分子。此外，拟南芥素还与包括癌症、心血管疾病和关节炎在内的疾病的发展和进展有关。前列腺素通过激活特异性G蛋白偶联受体（GPCR）发挥作用。在这份报告中，我们研究了前列腺素F2α受体（FP）信号作为软骨细胞分化调节剂的作用。我们发现，FP的表达显着诱导软骨细胞的分化过程中，并在软骨上调。FP在ATDC 5软骨细胞系中的强制表达导致分化相关基因的表达增加和细胞外基质（ECM）的合成增加，而不管胰岛素的存在。类似地，PGF 2 α处理诱导软骨形成标记基因的表达。相反，内源性FP表达的敲低抑制了软骨细胞标记基因的表达和ECM的合成。软骨胚的器官培养显示PGF 2 α诱导软骨细胞肥大。此外，FP过表达增加了Bmp-6、磷酸化Smad 1/5和Bmpr 1a的水平，而FP敲低降低了这些基因的表达。这些结果表明，FP表达的上调在软骨细胞分化中起重要作用，并调节BMP信号。
Prostaglandins are a group of lipid signaling molecules involved in various physiological processes. In addition, prostaglandins have been implicated in the development and progression of diseases including cancer, cardiovascular disease, and arthritis. Prostaglandins exert their effects through the activation of specific G protein-coupled receptors (GPCRs). In this report, we examined the role of prostaglandin F2α receptor (FP) signaling as a regulator of chondrocyte differentiation. We found that FP expression was dramatically induced during the differentiation of chondrocytes and was up-regulated in cartilages. Forced expression of FP in ATDC5 chondrogenic cell line resulted in the increased expression of differentiation-related genes and increased synthesis of the extracellular matrix (ECM) regardless of the presence of insulin. Similarly, PGF2α treatment induced the expression of chondrogenic marker genes. In contrast, knockdown of endogenous FP expression suppressed the expression of chondrocyte marker genes and ECM synthesis. Organ culture of cartilage rudiments revealed that PGF2α induces chondrocyte hypertrophy. Additionally, FP overexpression increased the levels of Bmp-6, phospho-Smad1/5, and Bmpr1a, while knockdown of FP reduced expression of those genes. These results demonstrate that up-regulation of FP expression plays an important role in chondrocyte differentiation and modulates Bmp signaling.
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DOI：
10.1242/dev.029926
发表时间：
2009-04
期刊：
Development (Cambridge, England)
影响因子：
--
作者：
Retting KN;Song B;Yoon BS;Lyons KM
通讯作者：
Lyons KM
影响因子：
1.5
作者：
Akiyama, H;Shukunami, C;Hiraki, Y
通讯作者：
Hiraki, Y
影响因子：
5.5
作者：
Jakob, M;Démarteau, O;Martin, I
通讯作者：
Martin, I
影响因子：
4
作者：
Hatakeyama, Y;Tuan, RS;Shum, L
通讯作者：
Shum, L
影响因子：
3.1
作者：
Altaf, F. M.;Hering, T. M.;Johnstone, B.
通讯作者：
Johnstone, B.