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.
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.
Huttunen
Minna M
MM
Calcium Research Unit, Department of Applied Chemistry and Microbiology, University of Helsinki, Helsinki, Finland. minna.huttunen@helsinki.fi
Pekkinen
Minna
M
Ahlström
Mikael E B
ME
Lamberg-Allardt
Christel J E
CJ
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*
D000597:Amino Acids, Branched-Chain; D007532:Isoleucine; D011392:Proline; D014633:Valine; D008239:Lysine