Effect of neurotrophin-4/5 on bone/cementum-related protein expressions and DNA synthesis in cultures of human periodontal ligament cells.
Effect of neurotrophin-4/5 on bone/cementum-related protein expressions and DNA synthesis in cultures of human periodontal ligament cells.
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DOI：
10.1902/jop.2008.070402
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发表时间：
2008-11
影响因子：
4.3
通讯作者：
N. Mizuno;H. Shiba;T. Inui;K. Takeda;M. Kajiya;Naohiko Hasegawa;H. Kawaguchi;H. Kurihara
中科院分区：
文献类型：
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作者：
N. Mizuno;H. Shiba;T. Inui;K. Takeda;M. Kajiya;Naohiko Hasegawa;H. Kawaguchi;H. Kurihara
背景我们研究了神经营养素（NTs）作为牙周组织再生的信号分子，发现神经生长因子（NGF）和脑源性神经营养因子（BDNF）在体外调节人牙周膜（HPL）细胞的增殖和分化。本研究的目的是探讨NT-4/5是否也具有调节HPL细胞功能的能力。方法采用逆转录聚合酶链反应（RT-PCR）技术检测HPL细胞中NT-4/5及其高亲和力酪氨酸激酶受体（trk）B的mRNA表达。我们研究了NT-4/5如何调节HPL细胞培养物中骨/牙骨质相关蛋白（碱性磷酸酶[ALTH]、骨桥蛋白[OPN]、骨钙素[OC]和骨形态发生蛋白[BMP]-2）的mRNA表达。此外，还检测了NT-4/5对HPL细胞中钙化、OPN和OC的产生以及DNA合成的影响。结果HPL细胞表达NT-4/5和trkB mRNA; NT-4/5提高HPL细胞中ALPase、OPN、OC和BMP-2的mRNA水平以及OPN、OC和DNA的合成。PD 98059是一种细胞外信号调节激酶（ERK）抑制剂，可避免ALP 4、OPN、OC和BMP-2 mRNA水平的增加。NT-4/5增加磷酸化ERK 1/2的水平。此外，NT-4/5增强了HPL细胞培养物中矿物质沉积的量。结论NT-4/5与BDNF、NGF共同参与牙周膜细胞功能的调节。
BACKGROUND We studied neurotrophins (NTs) as signaling molecules for periodontal tissue regeneration and showed that nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) modulate the proliferation and differentiation of human periodontal ligament (HPL) cells in vitro. The purpose of this study was to investigate whether NT-4/5 also has the ability to regulate the function of HPL cells. METHODS mRNA expressions of NT-4/5 and its high-affinity tyrosine kinase receptor (trk)B were analyzed in HPL cells by reverse transcription-polymerase chain reaction. We examined how NT-4/5 regulates the mRNA expression of bone/cementum-related proteins (alkaline phosphatase [ALPase], osteopontin [OPN], osteocalcin [OC], and bone morphogenetic protein [BMP]-2) in cultures of HPL cells. Moreover, the effects of NT-4/5 on calcification, the production of OPN and OC, and DNA synthesis in HPL cells were examined. RESULTS NT-4/5 and trkB mRNA were expressed in HPL cells. NT-4/5 elevated the mRNA levels of ALPase, OPN, OC, and BMP-2 and the syntheses of OPN, OC, and DNA in HPL cells. PD98059, an extracellular signal-regulated kinase (ERK) inhibitor, obviated the increase in the mRNA levels of ALPase, OPN, OC, and BMP-2. NT-4/5 increased the levels of phosphorylated ERK1/2. Furthermore, NT-4/5 enhanced the amount of mineral deposits in cultures of HPL cells. CONCLUSION NT-4/5, as well as BDNF and NGF, is suggested to play a role in the regulation of function of periodontal ligament cells.