Regeneration of bone and periodontal ligament induced by recombinant amelogenin after periodontitis.

Regeneration of bone and periodontal ligament induced by recombinant amelogenin after periodontitis.
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DOI:
10.1111/j.1582-4934.2009.00700.x
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发表时间:
2009-06
影响因子:
5.3
通讯作者:
Deutsch D
Deutsch D
中科院分区:
医学2区
文献类型:
--
作者:
Haze A;Taylor AL;Haegewald S;Leiser Y;Shay B;Rosenfeld E;Gruenbaum-Cohen Y;Dafni L;Zimmermann B;Heikinheimo K;Gibson CW;Fisher LW;Young MF;Blumenfeld A;Bernimoulin JP;Deutsch D

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受慢性疾病影响的矿化组织再生是一项重大的科学和临床挑战。牙周炎就是这样一种常见疾病,它涉及牙齿支持组织、牙槽骨、牙周韧带和牙骨质的破坏,常常导致牙齿脱落。1997年,人们清楚地认识到,疏水性外胚层釉质基质蛋白(EMPs)除了在釉质形成中起作用外,还在这些牙周组织的再生中发挥作用。上皮EMPs是由多个基因编码的多肽的异质混合物。然而,不清楚这些众多的EMPs中哪一种诱导再生以及涉及哪些机制。在此我们表明,在犬模型中制造实验性牙周炎后,一种单一的重组人釉原蛋白(rHAM +)可诱导所有牙齿支持组织的体内再生。为了进一步了解再生过程,在牙槽骨(骨细胞、成骨细胞和破骨细胞)、牙周韧带、牙骨质的正常和再生细胞以及骨髓基质细胞中检测到了釉原蛋白的表达。釉原蛋白在骨转换和活性高的区域表达最高。进一步的研究表明,在应用后的前两周,rHAM +直接或间接诱导大量间充质祖细胞募集,这些细胞后来分化形成再生的牙周组织。一种单一蛋白质通过募集间充质祖细胞,以正确的时空顺序实现所有牙周组织再生的能力,可为开发基于rHAM +的治疗牙周、骨和韧带疾病的新型治疗装置铺平道路。
Regeneration of mineralized tissues affected by chronic diseases comprises a major scientific and clinical challenge. Periodontitis, one such prevalent disease, involves destruction of the tooth-supporting tissues, alveolar bone, periodontal-ligament and cementum, often leading to tooth loss. In 1997, it became clear that, in addition to their function in enamel formation, the hydrophobic ectodermal enamel matrix proteins (EMPs) play a role in the regeneration of these periodontal tissues. The epithelial EMPs are a heterogeneous mixture of polypeptides encoded by several genes. It was not clear, however, which of these many EMPs induces the regeneration and what mechanisms are involved. Here we show that a single recombinant human amelogenin protein (rHAM+), induced in vivo regeneration of all tooth-supporting tissues after creation of experimental periodontitis in a dog model. To further understand the regeneration process, amelogenin expression was detected in normal and regenerating cells of the alveolar bone (osteocytes, osteoblasts and osteoclasts), periodontal ligament, cementum and in bone marrow stromal cells. Amelogenin expression was highest in areas of high bone turnover and activity. Further studies showed that during the first 2 weeks after application, rHAM+ induced, directly or indirectly, significant recruitment of mesenchymal progenitor cells, which later differentiated to form the regenerated periodontal tissues. The ability of a single protein to bring about regeneration of all periodontal tissues, in the correct spatio-temporal order, through recruitment of mesenchymal progenitor cells, could pave the way for development of new therapeutic devices for treatment of periodontal, bone and ligament diseases based on rHAM+.
DOI: 10.1007/bf00316294
发表时间: 1994-01-01
影响因子: 4.2
作者:
CATALANOSHERMAN, J;LASKOV, R;DEUTSCH, D
通讯作者: DEUTSCH, D
DOI: 10.1074/jbc.m306284200
发表时间: 2003-09-12
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发表时间: 2003-05-01
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DOI: 10.1177/154405910208100805
发表时间: 2002-08-01
影响因子: 7.6
作者:
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通讯作者: Knuutila, S
DOI: 10.1182/blood.v85.4.929.bloodjournal854929
发表时间: 1995-02-15
期刊: BLOOD
影响因子: 20.3
作者:
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通讯作者: SIMMONS, PJ