Regulatory mechanism of CCN2 production by serotonin (5-HT) via 5-HT2A and 5-HT2B receptors in chondrocytes.
Regulatory mechanism of CCN2 production by serotonin (5-HT) via 5-HT2A and 5-HT2B receptors in chondrocytes.
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DOI：
10.1371/journal.pone.0188014
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Takigawa M
中科院分区：
文献类型：
--
作者：
Hori A;Nishida T;Takashiba S;Kubota S;Takigawa M
5-羟色胺(5-羟色胺：5-HT)是中枢神经系统中的一种神经递质，在外周组织中也是全身血压的调节因子。最近，有报道5-HT2受体(5-HT2Rs)在缺乏血管和神经元的软骨组织中表达，提示5-HT2受体在软骨发育和再生过程中可能具有新的功能。我们先前的研究表明，CCN家族蛋白2/结缔组织生长因子(CCN2/CTGF)在软骨的发育和再生中起核心作用。因此，本研究旨在探讨5-羟色胺对软骨细胞产生CCN2的影响。首先，我们发现5-HT2R亚型5-HT2AR和5-HT2BR的mRNAs在人软骨细胞系HCS-2/8中有表达，但没有检测到5-HT2CRmRNA。外源性加入5-羟色胺不影响5-HT2AR和5-HT2BR的表达。接下来，我们证明了5-HT2AR激动剂以及5-羟色胺和5-HT2BR拮抗剂联合使用可以增加CCN2的产量。相反，5-HT2BR激动剂以及5-羟色胺和5-HT2AR拮抗剂联合使用可减少CCN2的产生。此外，我们还发现，5-HT2AR激动剂使Akt和p38MAPK的磷酸化增加，而PKCε、PKCζ、ERK1/2和JNK的磷酸化增加。最后，我们发现5-HT2AR定位于生长板，而5-HT2BR定位于关节软骨。这些结果表明，5-羟色胺通过生长板中的5-HT2AR促进CCN2的产生，而通过关节软骨中的5-HT2BR抑制CCN2的产生，以促进长骨的协调发展。
Serotonin (5-hydroxytryptamine: 5-HT) is recognized as a neurotransmitter in the central nerve system and as a regulator of systemic blood pressure in the peripheral tissues. Recently, it was reported that 5-HT2 receptors (5-HT2Rs) were expressed in cartilage tissues lacking both vessels and neurons, suggesting possible novel functions of 5-HT during cartilage development and regeneration. Our previous data indicated that CCN family protein 2/connective tissue growth factor (CCN2/CTGF) plays a central role in cartilage development and regeneration. Therefore, the aim of this study was to investigate the effect of 5-HT on the production of CCN2 in chondrocytes. Firstly, we showed that the mRNAs of 5-HT2R subtypes 5-HT2AR and 5-HT2BR, were expressed in a human chondrocytic cell line, HCS-2/8; however, 5-HT2CR mRNA was not detected. In addition, exogenously added 5-HT did not affect the 5-HT2AR and 5-HT2BR expressions. Next, we demonstrated that CCN2 production was increased by treatment with a 5-HT2AR agonist and the combination of 5-HT and 5-HT2BR antagonist. In contrast, treatment with a 5-HT2BR agonist and the combination of 5-HT and 5-HT2AR antagonist decreased CCN2 production. Furthermore, we showed that phosphorylation of Akt and p38 MAPK were increased by treatment with 5-HT2AR agonist, and that phosphorylation of PKCε, PKCζ, ERK1/2 and JNK were increased by treatment with 5-HT2BR agonist. Finally, we found that 5-HT2AR was localized in the growth plate, whereas 5-HT2BR was localized in the articular cartilage. These findings suggest that 5-HT promotes CCN2 production through the 5-HT2AR in growth plates, and that it represses CCN2 production through the 5-HT2BR in articular cartilage for harmonized development of long bones.
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影响因子：
6.2
作者：
Nishida, T;Kubota, S;Takigawa, M
通讯作者：
Takigawa, M
影响因子：
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影响因子：
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DOI：
10.1016/j.pnpbp.2008.08.020
发表时间：
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影响因子：
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作者：
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通讯作者：
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DOI：
10.1124/jpet.115.228395
发表时间：
2016-04-01
影响因子：
3.5
作者：
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通讯作者：
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