Differential Effect of Amelogenin Peptides on Osteogenic Differentiation In Vitro: Identification of Possible New Drugs for Bone Repair and Regeneration
Differential Effect of Amelogenin Peptides on Osteogenic Differentiation In Vitro: Identification of Possible New Drugs for Bone Repair and Regeneration
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DOI：
10.1089/ten.tea.2011.0375
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发表时间：
2012-06-01
影响因子：
4.1
通讯作者：
Donos, Nikolaos
中科院分区：
文献类型：
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作者：
Amin, Harsh D.;Olsen, Irwin;Donos, Nikolaos
釉质基质蛋白(EMP)可促进牙周膜和牙根骨质的再生，在体外可促进骨形成细胞的分化，在体内可促进新骨的生长。然而，已报道的EMP对骨再生的不一致和不可预测的影响可能是由于这种异质材料的高度不同的组成，主要由釉原蛋白和釉原蛋白衍生的多肽组成。因此，本研究考察了Emdogain(R)(EMD；Institut Strutaann，瑞士巴塞尔)的天然低分子(LMW)和高分子(HMW)部分对体外骨前体细胞成骨分化的影响。EMD是一种商业形式的EMP。此外，还研究了化学合成的LMW和HMW的特定成分，即富含酪氨酸的釉原蛋白多肽(TRAP)和亮氨酸富含釉原蛋白的异构体(LRAP)对成骨细胞活性的影响。我们的发现表明，虽然TRAP抑制了骨样矿化结节的形成，但LRAP上调了成骨分化。此外，人工合成的TRAP及其独特的C端12个氨基酸序列(TCT)也抑制了成骨细胞，而LRAP及其独特的C端23个氨基酸序列(LCT)显著促进了成骨细胞的终末分化。这些发现表明，EMP中存在的釉原蛋白衍生多肽序列的不同效应可能具有潜在的临床价值，新的具有生物活性的TCT多肽是限制病理性骨细胞生长的有用工具，而独特的LCT序列在牙周和骨科疾病的治疗中具有治疗效果。
Enamel matrix proteins (EMP) have been shown to promote regeneration of periodontal ligament and root cementum, and sometimes to enhance the differentiation of bone-forming cells in vitro and new bone growth in vivo. However, the inconsistent and unpredictable effects of EMP that have been reported for bone regeneration may be due to the highly variable composition of this heterogeneous material, which is comprised mainly of amelogenin and amelogenin-derived peptides. The present study has therefore examined the effects of naturally occurring low-molecular-weight (LMW) and high-molecular-weight (HMW) fractions of Emdogain (R) (EMD; Institut Straumann, Basel, Switzerland), a commercially available form of EMP, on osteogenic differentiation of bone precursor cells in vitro. In addition, the effects of chemically synthesized specific components of LMW and HMW-namely, the tyrosine-rich amelogenin peptide (TRAP), a specific amelogenin isoform derived by proteolytic clipping, and a leucine-rich amelogenin peptide (LRAP), an isoform derived by alternative splicing-on bone-forming cell activity were also investigated. Our findings demonstrate that while TRAP suppressed the formation of bone-like mineralized nodules, LRAP upregulated osteogenic differentiation. Furthermore, synthetically produced TRAP and its unique C-terminal 12 amino acid sequence (TCT) also suppressed bone-forming cells, whereas LRAP and its unique C-terminal 23 amino acid sequence (LCT) markedly enhanced terminal differentiation of bone-forming cells. These findings suggest that the differential effects of amelogenin-derived peptide sequences present in EMP could be of potential clinical value, with the novel bioactive TCT peptide as a useful tool for limiting pathological bone cell growth and the unique LCT sequence having therapeutic benefits in the treatment of periodontal and orthopedic diseases.