Collagen hydrolysates increased osteogenic gene expressions via a MAPK signaling pathway in MG-63 human osteoblasts.
The present study investigated the effects of CHs on osteogenic activities and MAPK-regulation on bone matrix gene expressions. The effects of CHs on cell proliferation, alkaline phosphatase (ALP) 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 was examined using Western blot analysis. The expressions of osteogenic genes were measured by quantitative real-time PCR. CHs dose-dependently increased MG-63 cell proliferation, ALP activity, collagen synthesis, and calcium deposition. CHs activated ERK1/2, JNK1/2, p38, and ELK1 phosphorylation except cJUN. The COL1A1 (collagen, type I, alpha 1), ALPL (alkaline phosphatase), BGLAP (osteocalcin), and SPP1 (secreted phosphoprotein 1, osteopontin) gene expressions were increased by CH treatment. The ERK1/2 inhibitor (PD98509) blocked the CH-induced COL1A1 and ALPL gene expression, as well as ELK1 phosphorylation. The JNK1/2 inhibitor (SP600125) abolished CH-induced COL1A1 expression. The p38 inhibitor (SB203580) blocked CH-induced COL1A1 and SPP1 gene expression. In conclusion, CH treatment stimulates the osteogenic activities and increases bone matrix gene expressions via the MAPK/ELK1 signaling pathway. These results could provide a mechanistic explanation for the bone-strengthening effects of CHs.
Department of Food & Biotechnology, Hanseo University, Seosan, Chungnam 356-706, South Korea.
Hye Kyung
HK
Kim
Myung-Gyou
MG
Kim
Kang-Hyun
KH
Leem
D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation; D003094:Collagen / Q000737:chemistry / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D010766:Phosphorylation; D011492:Protein Hydrolysates / Q000737:chemistry / Q000378:metabolism*; D015854:Up-Regulation
D011492:Protein Hydrolysates; D003094:Collagen; D048052:Mitogen-Activated Protein Kinase 3; D000469:Alkaline Phosphatase