title: Long-term effects of tripeptide Ile-Pro-Pro on osteoblast differentiation in vitro.
abstract: Bone mineralization is a result of the function of bone-forming osteoblasts. Osteoblast differentiation from their precursors is a carefully controlled process that is affected by many signaling molecules. Protein-rich food-derived bioactive peptides are reported to express a variety of functions in vivo. We studied the long-term in vitro effect of bioactive tripeptide Ile-Pro-Pro (IPP) on osteoblasts differentiated from human mesenchymal stem cells. Osteoblast bone alkaline phosphatase activity (bALP), bone-forming capacity and gene expression were investigated. Treatment with 50 microM IPP had no effect on bALP activity, but osteoblast mineralization was increased. Gene expression of beta-catenin, Cbfa1/Runx2, PTHrP, CREB-5, osteoglycin, osteocalcin, caspase-8, osteoprotegerin (OPG) and RANKL was analyzed by quantitative real-time PCR on Days 13, 17 and 20 of culture. The results indicate that IPP increased mineral formation due to enhanced cell survival and matrix formation. In addition, IPP reduced the RANKL/OPG ratio. Bioactive peptides, such as IPP, could be one method by which a protein-rich diet promotes bone integrity.
authors.affiliation: Calcium Research Unit, Department of Applied Chemistry and Microbiology, University of Helsinki, P.O. Box 66, 00014 Helsinki, Finland. minna.huttunen@helsinki.fi
authors.forename: Minna M
authors.initials: MM
authors.lastname: Huttunen
authors.forename: Minna
authors.initials: M
authors.lastname: Pekkinen
authors.forename: Mikael E B
authors.initials: ME
authors.lastname: Ahlström
authors.forename: Christel J E
authors.initials: CJ
authors.lastname: Lamberg-Allardt
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D001483:Base Sequence; D001842:Bone and Bones / Q000201:enzymology; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D017931:DNA Primers; D006801:Humans; D066298:In Vitro Techniques; D008903:Minerals / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology*; D010006:Osteoblasts / Q000187:drug effects*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D008903:Minerals; D009842:Oligopeptides; C489032:isoleucyl-prolyl-proline; D000469:Alkaline Phosphatase