PMID- 22429009 OWN - NLM STAT- MEDLINE DCOM- 20120926 LR - 20181201 IS - 1937-335X (Electronic) IS - 1937-3341 (Linking) VI - 18 IP - 11-12 DP - 2012 Jun TI - Effect of enamel matrix derivative and of proline-rich synthetic peptides on the differentiation of human mesenchymal stem cells toward the osteogenic lineage. PG - 1253-63 LID - 10.1089/ten.tea.2011.0404 [doi] AB - With the aim of discovering new molecules for induction of bone formation and biomineralization, combination of bioinformatics and simulation methods were used to design the structure of artificial peptides based on proline-rich domains of enamel matrix proteins. In this study, the effect of such peptides on the differentiation toward the osteogenic lineage of human umbilical cord mesenchymal stem cells (hUCMSCs) was evaluated with or without osteogenic supplements (hydrocortisone, beta-glycerol phosphate, and ascorbic acid) and compared to the effect of the commercially available enamel matrix derivative (EMD). It was hypothesized that the differentiation toward the osteogenic lineage of hUCMSCs would be promoted by the treatment with the synthetic peptides when combined with differentiation media, or it could even be directed exclusively by the synthetic peptides. Osteoinductivity was assessed by cell proliferation, bone morphogenetic protein-2 secretion, and gene expression of osteogenic markers after 1, 3, and 14 days of treatment. All peptides were safe with the dosages used, showing lower cell toxicity. P2, P4, and P6 reduced cell proliferation with growing media by 10%-15%. Higher expression of early osteoblast markers was found after 3 days of treatment with EMD in combination with osteogenic supplements, while after 14 days of treatment, cells treated by the different synthetic peptides in combination with osteogenic supplements showed higher osteocalcin mRNA levels. We can conclude that osteogenic differentiation of hUCMSCs is promoted by short-term EMD treatment in combination with osteogenic supplements and by long-term treatment by the synthetic peptides in combination with osteogenic supplements, showing similar results for all the peptide variants analyzed in this study. FAU - Ramis, Joana Maria AU - Ramis JM AD - Group of Cell Therapy and Tissue Engineering, Research Institute on Health Sciences-IUNICS, University of the Balearic Islands, Palma de Mallorca, Spain. FAU - Rubert, Marina AU - Rubert M FAU - Vondrasek, Jiri AU - Vondrasek J FAU - Gaya, Antoni AU - Gaya A FAU - Lyngstadaas, Staale Petter AU - Lyngstadaas SP FAU - Monjo, Marta AU - Monjo M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120319 PL - United States TA - Tissue Eng Part A JT - Tissue engineering. Part A JID - 101466659 RN - 0 (Biomarkers) RN - 0 (Bone Morphogenetic Protein 2) RN - 0 (Culture Media) RN - 0 (Dental Enamel Proteins) RN - 0 (Peptides) RN - 0 (RNA, Messenger) RN - 0 (enamel matrix proteins) RN - 9DLQ4CIU6V (Proline) RN - EC 1.1.1.27 (L-Lactate Dehydrogenase) SB - IM MH - Amino Acid Sequence MH - Biomarkers/metabolism MH - Bone Morphogenetic Protein 2/metabolism MH - Cell Differentiation/*drug effects MH - Cell Lineage/*drug effects MH - Cell Proliferation/drug effects MH - Cell Survival/drug effects MH - Culture Media MH - Dental Enamel Proteins/*chemistry MH - Gene Expression Regulation/drug effects MH - Humans MH - L-Lactate Dehydrogenase/metabolism MH - Mesenchymal Stem Cells/*cytology/drug effects/enzymology MH - Models, Molecular MH - Molecular Sequence Data MH - Osteogenesis/*drug effects/genetics MH - Peptides/chemistry/*pharmacology MH - Proline/*chemistry MH - RNA, Messenger/genetics/metabolism EDAT- 2012/03/21 06:00 MHDA- 2012/09/27 06:00 CRDT- 2012/03/21 06:00 PHST- 2012/03/21 06:00 [entrez] PHST- 2012/03/21 06:00 [pubmed] PHST- 2012/09/27 06:00 [medline] AID - 10.1089/ten.tea.2011.0404 [doi] PST - ppublish SO - Tissue Eng Part A. 2012 Jun;18(11-12):1253-63. doi: 10.1089/ten.tea.2011.0404. Epub 2012 Mar 19.