Neurotrophins in cultured cells from periodontal tissues

Neurotrophins in cultured cells from periodontal tissues
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DOI:
10.1902/jop.2003.74.1.76
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发表时间:
2003-01-01
影响因子:
4.3
通讯作者:
Shiba, H
Shiba, H
中科院分区:
医学2区
文献类型:
--
作者:
Kurihara, H;Shinohara, H;Shiba, H

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本文综述了神经营养因子及其受体的基本功能,并根据近年来培养的人牙周组织细胞的资料,讨论了神经营养因子及其特异性受体的表达和功能。神经营养因子、神经生长因子(NGF)、脑源性神经营养因子(BDNF)和神经营养因子-3 (NT-3)在神经细胞的分化和存活中起着至关重要的作用。神经营养素激活2种不同的受体:原肌球蛋白相关激酶(Trk)家族的酪氨酸受体(TrkA, TrkB和TrkC)和p75受体,p75受体是肿瘤坏死因子受体超家族的成员。神经营养因子通过激活Trk受体和/或p75神经营养因子受体调节细胞死亡和细胞存活。据报道,神经营养因子也可以由非神经元细胞产生,如白细胞、成骨细胞或成纤维细胞,并以许多其他方式作用于非神经元细胞。神经营养因子在骨折愈合过程中的表达特别有趣,神经营养因子现在与硬组织再生有关。众所周知,神经营养因子及其受体在牙齿发育过程中表达。近年来的研究发现,神经营养因子和Trk受体在小鼠成骨细胞系中有表达。人牙周韧带细胞、人牙龈成纤维细胞和人牙龈角质形成细胞表达NGF和TrkA mRNA。用PC12细胞(大鼠肾上腺嗜铬细胞瘤细胞)进行生物测定,证实人牙周韧带细胞和牙龈角质形成细胞分泌具有生物活性的NGF肽。NGF和TrkA mRNA的表达受白细胞介素(IL)1 β的调控。NGF增加人牙周韧带细胞DNA合成和骨相关蛋白、碱性磷酸酶和骨桥蛋白mRNA表达。神经营养因子和Trk受体在人牙周组织中的表达可能通过局部自分泌和旁分泌途径促进牙周组织的再生和神经支配。最近的研究表明,神经营养因子和Trk受体的一些功能与牙周疾病和牙周组织再生有关。然而,需要进行体内研究来阐明神经营养因子及其受体(包括p75)在牙周病和牙周组织再生中的作用。
We review the basic functions of neurotrophins and their receptors and discuss the expression and functions of neurotrophins and their specific receptors based on recent data using cultured cells from human periodontal tissues. Neurotrophins, nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3) play crucial roles in the differentiation and survival of neural cells. Neurotrophins activate 2 different receptor classes: the tropomyosin-related kinase (Trk) family of receptor tyrosine kinases (TrkA, TrkB, and TrkC) and the p75 receptor, a member of the tumor necrosis factor receptor superfamily. Neurotrophins regulate both cell death and cell survival through activations of Trk receptors and/or p75 neurotrophin receptor. It has been reported that neurotrophins are also produced from non-neuronal cells, such as leukocytes, osteoblasts, or fibroblasts, and act in many other ways on non-neuronal cells. Neurotrophin expression during bone fracture healing is especially interesting, and neurotrophins are now implicated in hard tissue regeneration. It is well known that neurotrophins and their receptors are expressed in tooth development. Recent studies have found that neurotrophins and Trk receptors are expressed in mouse osteoblastic cell lines. Human periodontal ligament cells, human gingival fibroblasts, and human gingival keratinocytes expressed mRNA for NGF and TrkA. The secretion of bioactive NGF peptides from human periodontal ligament cells and human gingival keratinocytes was confirmed by bioassay using PC12 cells (rat adrenal pheochromocytoma cells). The expression of NGF and TrkA mRNA was regulated by interleukin (IL)1beta. NGF increased DNA synthesis and expressions of mRNA for bone-related proteins, alkaline phosphatase, and osteopontin in human periodontal ligament cells. Neurotrophins and Trk receptors expressed in human periodontal tissue may contribute to regeneration as well as innervation of periodontal tissue through local autocrine and paracrine pathways. Recent data suggest that some functions of neurotrophins and Trk receptors relate to periodontal disease and periodontal tissue regeneration. However, in vivo studies will be required to clarify the roles of neurotrophins and their receptors, including p75, in periodontal disease and periodontal tissue regeneration.