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Differential regulation of platelet‐derived growth factor stimulated migration and proliferation in osteoblastic cells
Author(s) -
Mehrotra Meenal,
Krane Stephen M.,
Walters Kristen,
Pilbeam Carol
Publication year - 2004
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.20138
Subject(s) - microbiology and biotechnology , platelet derived growth factor receptor , mapk/erk pathway , growth factor , cell growth , cell migration , mitogen activated protein kinase , p38 mitogen activated protein kinases , platelet derived growth factor , kinase , signal transduction , chemistry , biology , cell , biochemistry , receptor
Osteoblastic migration and proliferation in response to growth factors are essential for skeletal development, bone remodeling, and fracture repair, as well as pathologic processes, such as metastasis. We studied migration in response to platelet‐derived growth factor (PDGF, 10 ng/ml) in a wounding model. PDGF stimulated a twofold increase in migration of osteoblastic MC3T3‐E1 cells and murine calvarial osteoblasts over 24–48 h. PDGF also stimulated a tenfold increase in 3 H‐thymidine ( 3 H‐TdR) incorporation in MC3T3‐E1 cells. Migration and DNA replication, as measured by BrdU incorporation, could be stimulated in the same cell. Blocking DNA replication with aphidicolin did not reduce the distance migrated. To examine the role of mitogen‐activated protein (MAP) kinases in migration and proliferation, we used specific inhibitors of p38 MAP kinase, extracellular signal regulated kinase (ERK), and c‐Jun N‐terminal kinase (JNK). For these signaling studies, proliferation was measured by carboxyfluorescein diacetate succinimidyl ester (CFSE) using flow cytometry. Inhibition of the p38 MAP kinase pathway by SB203580 and SB202190 blocked PDGF‐stimulated migration but had no effect on proliferation. Inhibition of the ERK pathway by PD98059 and U0126 inhibited proliferation but did not inhibit migration. Inhibition of JNK activity by SP600125 inhibited both migration and proliferation. Hence, the stimulation of migration and proliferation by PDGF occurred by both overlapping and independent pathways. The JNK pathway was involved in both migration and proliferation, whereas the p38 pathway was predominantly involved in migration and the ERK pathway predominantly involved in proliferation. © 2004 Wiley‐Liss, Inc.