Stretch-induced phosphorylation of ERK1/2 depends on differentiation stage of osteoblasts

被引:49
作者
Jansen, JHW
Weyts, FAA
Westbroek, I
Jahr, H
Chiba, H
Pols, HAP
Verhaar, JAN
van Leeuwen, JPTM
Weinans, H
机构
[1] Erasmus MC, Dept Orthopaed, Orthopaed Res Lab, NL-3000 DR Rotterdam, Netherlands
[2] Erasmus MC, Dept Internal Med, NL-3000 DR Rotterdam, Netherlands
[3] Sapporo Med Coll, Dept Pathol, Sapporo, Hokkaido, Japan
关键词
ERK1/2; stretch; mechanotransduction; human osteoblast; differentiation;
D O I
10.1002/jcb.20162
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The goal of this study was to investigate the effect of mechanical loading on osteoblasts and extracellular signal-regulated kinase (ERK 1/2) signaling in relation to osteoblast differentiation and mineralization. A human osteoblast cell line (SV-HFO) was triggered to differentiate to the advanced state of mineralization by addition of the osteogenic factors dexamethasone and beta-glycerophosphate. Osteoblasts were subjected to cyclic, equibiaxial stretch for 5, 15, or 60 min at different stages of differentiation (days 7, 14, and 21). Baseline (static) phosphorylated ERK1/2 and total ERK1/2 levels gradually increased during osteoblast differentiation. Cyclic stretch induced a rapid increase in ERK1/2 phosphorylation with a maximum between 5 and 15 min. Prolonged stretching for 60 min resulted in a decrease of phosphorylated ERK1/2 towards baseline level, suggesting a desensitization mechanism. The effect of stretch on ERK1/2 phosphorylation was strongest at later stages of differentiation (days 14 and 21). At day 21, the increase of ERK1/2 phosphorylation in response to stretch was significantly lower in non-differentiating than in differentiating osteoblasts. This could not be explained by differences in cell density, but did correlate with the formation of extracellular matrix, collagen fibrils. Mineralization of the extracellular matrix did not lead to a further increase of ERK1/2 phosphorylation. In conclusion, the current study demonstrates that the extent of activation of the ERK1/2 pathway is dependent on the differentiation or functional stage of the osteoblast. The presence of an extracellular matrix, but not per se mineralization, seems to be the predominant determinant of osteoblastic response to strain.
引用
收藏
页码:542 / 551
页数:10
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