PMID- 9712699 OWN - NLM STAT- MEDLINE DCOM- 19980911 LR - 20220331 IS - 0006-291X (Print) IS - 0006-291X (Linking) VI - 249 IP - 2 DP - 1998 Aug 19 TI - Proliferation and differentiation of human osteoblastic cells associated with differential activation of MAP kinases in response to epidermal growth factor, hypoxia, and mechanical stress in vitro. PG - 350-4 AB - In an attempt to elucidate the specificity of pathways from environmental stress to cellular outcome via mitogen activated protein kinases (MAPKs) activation, we examined the responsiveness of cultured human osteoblastic periodontal ligament (PDL) cells to epidermal growth factor (EGF), hypoxia, and mechanical stress, in terms of cell proliferation, differentiation, and associated activation of three different types of MAPK. Cell proliferation was promoted in the presence of 10ng/ml of EGF or in hypoxic conditions (5% O2), whereas it was inhibited by cyclic stretch (9% strain, 6 cycles/min), which was used as a model of mechanical stress. Conversely, the alkaline phosphatase activity, a marker for osteoblastic differentiation of the cells, was increased by cyclic stretch but decreased by EGF and hypoxia. The mitogenic response of PDL cells to EGF or hypoxia was associated with the selective phosphorylation and activation of extracellular-related kinase (ERK) 1/2, while phosphorylation and activation of c-Jun N-terminal kinase (JNK) was observed in mechanical stretch loaded cells. No such changes were seen in p38 protein. These findings suggested that stress-responsive changes in proliferation and osteoblastic differentiation of PDL cells are selectively mediated by ERK 1/2 and by JNK, respectively, and that a balance between these two pathways determines the cell fate. CI - Copyright 1998 Academic Press. FAU - Matsuda, N AU - Matsuda N AD - Nagasaki University Radioisotope Center, Nagasaki, Japan. FAU - Morita, N AU - Morita N FAU - Matsuda, K AU - Matsuda K FAU - Watanabe, M AU - Watanabe M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (Culture Media) RN - 0 (Nerve Tissue Proteins) RN - 62229-50-9 (Epidermal Growth Factor) RN - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases) RN - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) RN - EC 3.1.3.1 (Alkaline Phosphatase) SB - IM MH - Alkaline Phosphatase/metabolism MH - Calcium-Calmodulin-Dependent Protein Kinases/*metabolism MH - *Cell Differentiation MH - *Cell Division MH - *Cell Hypoxia MH - Cells, Cultured MH - Culture Media MH - Enzyme Activation MH - Epidermal Growth Factor/*pharmacology MH - Humans MH - JNK Mitogen-Activated Protein Kinases MH - Mitogen-Activated Protein Kinases/metabolism MH - Nerve Tissue Proteins/metabolism MH - Osteoblasts/*cytology/enzymology MH - Periodontal Ligament MH - Phosphorylation MH - Stress, Mechanical EDAT- 1998/08/26 00:00 MHDA- 1998/08/26 00:01 CRDT- 1998/08/26 00:00 PHST- 1998/08/26 00:00 [pubmed] PHST- 1998/08/26 00:01 [medline] PHST- 1998/08/26 00:00 [entrez] AID - S0006-291X(98)99151-3 [pii] AID - 10.1006/bbrc.1998.9151 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 1998 Aug 19;249(2):350-4. doi: 10.1006/bbrc.1998.9151.