Abstract

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Title:: Increased expression of BMP7 by fluid shear stress mediated through NFATc1-ERK5 pathway

Author(s):: DING Ning1; 2; YAN Liang1; 2; WAN Lang1; 2; XIA Yayi1; 2; 1. Institute of Orthopedics, Lanzhou University Second Hospital, Lanzhou 730000, China; 2. Key Laboratory for Orthopedics of Gansu Province, Lanzhou 730000, China

Keywords:: ; nuclear factor of activated T cells c1; extracellular-regulated protein kinase 5; bone morphogenetic protein 7; fluid shear stress; osteoblast

Abstract:: Objective To discuss the interrelation between nuclear factor of activated T cells c1 (NFATc1) and extracellular-regulated protein kinase 5 (ERK5), and explore the fluid shear stress (FSS)-induced signal pathway that regulates the expression of bone morphogenetic protein 7 (BMP7). Methods The experiment was divided into 6 groups, namely control group, FSS group, CsA (Cyclosporin, NFATc1 inhibitor) group, XMD8-92 (ERK5 inhibitor) group, FSS+CsA group, and FSS+XMD8-92 group. Western Blot was applied to access the expression level of NFATc1, ERK5, p-ERK5 and BMP7. Results 12 dyn/cm2 FSS for 45 min well promoted the level of NFATc1 and p-ERK5 in osteoblasts. 400 nmol/L CsA for 30 min effectively inhibited the expression of NFATc1 and the phosphorylation of ERK5, but 5 μmol/L XMD8-92 for 1 h only blocked the phosphorylation of ERK5, without causing effects on NFATc1. The expression level of BMP7 in MC3T3-E1 cell was promoted by FSS, and either CsA or XMD8-92 significantly inhibited the expression of BMP7. Conclusion FSS mediates the phosphorylation of ERK5 in osteoblasts by NFATc1, and BMP7 regarded as downstream target of ERK5 was regulated by NFATc1-ERK5 pathway.