Abstract
The present study investigated the effects of egg yolk-derived peptide (YPEP) on osteogenic activities and MAPK-regulation of osteogenic gene expressions. The effects of YPEP on cell proliferation, alkaline phosphatase activity, collagen synthesis, and mineralization were measured in human osteoblastic MG-63 cells. Activation of MAPKs and downstream transcription factors such as extracellular-signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase 1/2 (JNK1/2), p38, ELK1, and cJUN were examined using western blot analysis. YPEP dose-dependently increased MG-63 cell proliferation, ALP activity, collagen synthesis, and calcium deposition. YPEP activated ERK1/2, p38, and ELK1 phosphorylation whereas JNK and cJUN were not affected by YPEP. The COL1A1 (collagen, type I, alpha 1), ALPL (alkaline phosphatase), and SPP1 (secreted phosphoprotein 1, osteopontin) gene expressions were increased while BGLAP (osteocalcin) was not affected by YPEP. The ERK1/2 inhibitor (PD98509) blocked the YPEP-induced COL1A1 and ALPL gene expressions as well as ELK1 phosphorylation. The p38 inhibitor (SB203580) blocked YPEP-induced COL1A1 and ALPL gene expressions. SPP1 gene expression was not affected by these MAPK inhibitors. In conclusion, YPEP treatment stimulates the osteogenic differentiation via the MAPK/ELK1 signaling pathway. These results could provide a mechanistic explanation for the bone-strengthening effects of YPEP.
Highlights
Eggs have long been an important contributor to the nutritional quality of the human diet, and recognized as a very valuable source of proteins for human nutrition
We demonstrate that yolk-derived peptide (YPEP) promotes the mRNA expressions of osteogenic genes through a mitogen-activated protein kinase (MAPK)/ELK1 signaling pathway
The effects of YPEP on the differentiation of MG-63 cells were examined by determining alkaline phosphatase (ALP) activity, collagen synthesis, and mineralization
Summary
Eggs have long been an important contributor to the nutritional quality of the human diet, and recognized as a very valuable source of proteins for human nutrition. We have previously reported that egg yolk water-soluble protein (YSP) stimulates proliferation, differentiation, and mineralization of osteoblasts [2]. Many previous studies have shown that the expression of osteoblastogenic genes and functions are stimulated by mitogen-activated protein kinase (MAPK). Activated ERK1/2 and p38 phosphorylate many substrates, including ELK1 [17], leading to increased c-fos transcriptional activity. The phosphorylation of ELK1 transforms this protein into a potent trans-activator of transcription, the MAPK/ELK1 cassette plays a major role in signaling-driven gene activation [19]. Egg yolk-derived peptide (YPEP) was prepared, and its effects on proliferation, differentiation and mineralization of human osteoblastic MG-63 cells were explored. We demonstrate that YPEP promotes the mRNA expressions of osteogenic genes through a MAPK/ELK1 signaling pathway
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