title: Effects of bioactive peptides isoleucine-proline-proline (IPP), valine-proline-proline (VPP) and leucine-lysine-proline (LKP) on gene expression of osteoblasts differentiated from human mesenchymal stem cells.
abstract: Food-derived bioactive peptides are reported to express a variety of functions in vivo. We studied the in vitro effect of three bioactive tripeptides, isoleucine-proline-proline (IPP), valine-proline-proline (VPP) and leucine-lysine-proline (LKP), on osteoblast proliferation and gene expression. We used UMR-106 osteosarcoma cells, human marrow-derived mesenchymal stem cells (hMSC) and osteoblasts differentiated from hMSC. Treatment with 50 mum-IPP increased UMR-106 cell and hMSC proliferation. The gene expression of hMSC-differentiated osteoblasts was analysed by the microarray method. Microarray analysis revealed that IPP up-regulated 270 genes and down-regulated 100 genes. VPP and LKP, by contrast, had a very modest influence on osteoblast gene expression. Real-time PCR confirmed that IPP up-regulated PTHrP, BMP-5 and CREB-5 and down-regulated VDR and caspase-8. IPP possesses potential to increase osteoblast proliferation, differentiation and signalling. Agents that increase the number and function of osteoblasts could improve bone mass and structure, and decrease fracture risk.
authors.affiliation: Calcium Research Unit, Department of Applied Chemistry and Microbiology, University of Helsinki, 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: D000597:Amino Acids, Branched-Chain / Q000737:chemistry; D001854:Bone Marrow Cells / Q000187:drug effects*; D002454:Cell Differentiation / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006801:Humans; D007532:Isoleucine / Q000494:pharmacology*; D008239:Lysine / Q000494:pharmacology*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000187:drug effects*; D010006:Osteoblasts / Q000166:cytology; D010012:Osteogenesis / Q000235:genetics; D011392:Proline / Q000494:pharmacology*; D014633:Valine / Q000494:pharmacology*
chemical_list: D000597:Amino Acids, Branched-Chain; D007532:Isoleucine; D011392:Proline; D014633:Valine; D008239:Lysine