Hemokinin-1 competitively inhibits substance P-induced stimulation of osteoclast formation and function
Hemokinin-1 competitively inhibits substance P-induced stimulation of osteoclast formation and function
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DOI：
10.1016/j.npep.2013.04.001
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发表时间：
2013-08-01
期刊：
影响因子：
2.9
通讯作者：
Yamaguchi, Kazunori
中科院分区：
文献类型：
--
作者：
Fukuda, Aya;Goto, Tetsuya;Yamaguchi, Kazunori
血激素-1(HK-1)是速激肽家族的新成员，由速激肽原4(TAC4)编码，与P物质(SP)共享神经激肽-1受体(NK1-R)。虽然HK-1被认为是一种内源性的外周SP样内分泌或旁分泌分子，但尚未研究HK-1在颌面部的分布和在骨组织中的作用。本研究观察了HK-1在三叉神经节和上颌骨中的分布，并探讨了HK-1在破骨细胞分化过程中的表达。在体内，采用Waldo法加载大鼠磨牙5d。在体外，从骨髓细胞中诱导出大鼠破骨细胞样细胞。免疫荧光染色和逆转录聚合酶链式反应(RT-PCR)检测HK-1的分布和表达。在体内，HK-1定位于大鼠三叉神经节神经元，但HK-1阳性神经元的数量少于SP阳性神经元。在上颌骨中，神经纤维、血管和骨细胞呈HK-1免疫阳性。此外，在受压侧破骨细胞内可见HK-1阳性免疫反应。体外聚合酶链式反应显示，TAC4和NK1-R在破骨细胞和骨髓细胞中均有表达。虽然SP(10(-7)M)处理导致破骨细胞数量增加，但HK-1(10-7M)处理不能。与未标记的SP和生物素标记的HK-1共同孵育后，与生物素标记的HK-1相比，生物素标记的HK-1多肽结合的破骨细胞数量明显减少。提示HK-1对破骨细胞的分化和功能可能无刺激作用。SP刺激的破骨细胞形成受外周血HK-1通过NK1-Rs竞争性调节。(C)2013爱思唯尔有限公司。保留所有权利。
Hemokinin-1 (HK-1) is a novel member of the tachykinin family that is encoded by preprotachykinin 4 (TAC4) and shares the neurokinin-1 receptor (NK1-R) with substance P (SP). Although HK-1 is thought to be an endogenous peripheral SP-like endocrine or paracrine molecule in locations where SP is not expressed, neither the distribution of HK-1 in the maxillofacial area nor the role HK-1 in bone tissue have been examined. In this study, we investigated the distribution of HK-1 in trigeminal ganglion (TG) and maxillary bone, and assessed the expression of HK-1 during osteoclast differentiation. In vivo, rat molars were loaded for 5 days using the Waldo method. In vitro, rat osteoclast-like cells were induced from bone marrow cells. HK-1 distribution and expression were examined by immunofluorescence staining and reverse transcription polymerase chain reaction (RT-PCR). In vivo, HK-1 was localized in rat TG neurons; however, the number of HK-1-positive neurons was less than that of SP-positive neurons. In the maxillary bone, nerve fibers, blood vessels, and osteocytes were immunopositive for HK-1. Furthermore, HK-1-positive immunoreactivity was found in osteoclasts on the pressure side. In vitro, PCR showed that TAC4 and NK1-R mRNA was expressed in osteoclasts as well as in bone marrow cells. Although SP (10(-7) M) treatment led to an increased number of osteoclasts, HK-1 (10-7 M) treatment did not. The numbers of biotin-labeled HK-1 peptides bound osteoclasts significantly decreased upon incubation with unlabeled SP and biotin-labeled HK-1 compared with biotin-labeled HK-1 alone. These results suggest that HK-1 may not stimulate the differentiation and function of osteoclasts. SP-stimulated osteoclast formation is competitively regulated by peripheral HK-1 through NK1-Rs. (C) 2013 Elsevier Ltd. All rights reserved.