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

• Published in: British journal of nutrition Vol. 98; no. 4; pp. 780 - 788
• Main Authors: Huttunen, Minna M., Pekkinen, Minna, Ahlström, Mikael E. B., Lamberg-Allardt, Christel J. E.
• Format: Journal Article
• Language: English
• Published: Cambridge, UK Cambridge University Press 01.10.2007
• Subjects: Amino Acids, Branched-Chain - chemistry; Bioactive peptide; Biological and medical sciences; Bone Marrow Cells - drug effects; Cell Differentiation - genetics; Dietary protein; Feeding. Feeding behavior; Female; Fundamental and applied biological sciences. Psychology; Gene Expression; Humans; IPP; Isoleucine - pharmacology; Lysine - pharmacology; Male; Mesenchymal Stromal Cells - drug effects; Osteoblast proliferation; Osteoblasts - cytology; Osteogenesis - genetics; Proline - pharmacology; Valine - pharmacology; Vertebrates: anatomy and physiology, studies on body, several organs or systems; IPP; Dietary protein; Bioactive peptide; Osteoblast proliferation; Human; Cell proliferation; Peptides; Stem cell; Proline; Leucine; Proliferation; Gene expression; Protein; Osteoarticular system; IPP: Osteoblast proliferation: Dietary protein: Bioactive peptide; Vertebrata; Mammalia; Lysine; Valine; Osteoblast; Bone; Isoleucine
• ISSN: 0007-1145; 1475-2662
• DOI: 10.1017/S0007114507744434

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 μm-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.