title: A tyrosine-rich amelogenin peptide promotes neovasculogenesis in vitro and ex vivo.
abstract: The formation of new blood vessels has been shown to be fundamental in the repair of many damaged tissues, and we have recently shown that the adult human periodontal ligament contains multipotent stem/progenitor cells that are capable of undergoing vasculogenic and angiogenic differentiation in vitro and ex vivo. Enamel matrix protein (EMP) is a heterogeneous mixture of mainly amelogenin-derived proteins produced during tooth development and has been reported to be sometimes effective in stimulating these processes, including in clinical regeneration of the periodontal ligament. However, the identity of the specific bioactive component of EMP remains unclear. In the present study we show that, while the high-molecular-weight Fraction A of enamel matrix derivative (a heat-treated form of EMP) is unable to stimulate the vasculogenic differentiation of human periodontal ligament cells (HPC) in vitro, the low-molecular-weight Fraction C significantly up-regulates the expression of the endothelial markers VEGFR2, Tie-1, Tie-2, VE-cadherin and vWF and markedly increases the internalization of low-density lipoprotein. Furthermore, we also demonstrate, for the first time, that the synthetic homolog of the 45-amino acid tyrosine-rich amelogenin peptide (TRAP) present in Fraction C is likely to be responsible for its vasculogenesis-inducing activity. Moreover, the chemically synthesized TRAP peptide is also shown here to be capable of up-regulating the angiogenic differentiation of the HPC, based on its marked stimulation of in vitro cell migration and tubule formation and of blood vessel formation assay in a chick embryo chorioallantoic membrane model ex vivo. This novel peptide, and modified derivatives, might thereby represent a new class of regenerative drug that has the ability to elicit new blood vessel formation and promote wound healing in vivo.
authors: Division of Biomaterials and Tissue Engineering, UCL Eastman Dental Institute, University College London, London, UK; Periodontology Unit, UCL Eastman Dental Institute, University College London, London, UK.
authors: Harsh D
authors: HD
authors: Amin
authors: Division of Biomaterials and Tissue Engineering, UCL Eastman Dental Institute, University College London, London, UK. Electronic address: i.olsen@ucl.ac.uk.
authors: Irwin
authors: I
authors: Olsen
authors: Division of Biomaterials and Tissue Engineering, UCL Eastman Dental Institute, University College London, London, UK; Department of Nanobiomedical Science & BK21 Plus NBM Global Reserch Center for Regenerative Medicine, Dankook University, Cheonan 330-714, Republic of Korea.
authors: Jonathan
authors: J
authors: Knowles
authors: PreClinical Research, Institut Straumann AG, Basel, Switzerland.
authors: Michel
authors: M
authors: Dard
authors: Periodontology Unit, UCL Eastman Dental Institute, University College London, London, UK. Electronic address: n.donos@ucl.ac.uk.
authors: Nikolaos
authors: N
authors: Donos
mesh_terms: D000135:Acid Phosphatase / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D053523:Amelogenin / Q000494:pharmacology*; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D002633:Chemotaxis / Q000187:drug effects; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000187:drug effects / Q000378:metabolism; D003746:Dental Enamel Proteins / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000235:genetics; D010513:Periodontal Ligament / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000071681:Tartrate-Resistant Acid Phosphatase; D014443:Tyrosine / Q000378:metabolism*; D055815:Young Adult; D014841:von Willebrand Factor / Q000378:metabolism; D000099152:Cadherin 5
chemical_list: D000135:Acid Phosphatase; D053523:Amelogenin; D015703:Antigens, CD; D015820:Cadherins; D003746:Dental Enamel Proteins; D007527:Isoenzymes; D000071681:Tartrate-Resistant Acid Phosphatase; D014443:Tyrosine; D014841:von Willebrand Factor; D000099152:Cadherin 5; C109069:enamel matrix proteins
keywords: Angiogenesis; Enamel matrix proteins; Ligament stem cells; Neovasculogenesis; Vasculogenesis