Fluid shear stress inhibits TNF-α-induced osteoblast apoptosis via ERK5 signaling pathway.
Fluid shear stress (FSS) is a potent mechanical stimulus and prevents cells from TNF-a-induced apoptosis. Recently, Extracellular-signal-regulated kinase 5 (ERK5) has been found to be involved in regulation of cell survival. However, little is known about the role of ERK5 signaling pathway in FSS-mediated anti-apoptotic effects in osteoblast. In this study, we show that FSS blocks TNF-a-induced apoptosis of MC3T3-E1 cells via ERK5 signaling pathway. We found that physiological FSS for 1 h significantly decreased TNF-α-induced MC3T3-E1 cells apoptosis. After inhibition of ERK5 activity by XMD8-92, a highly-selective inhibitor of ERK5 activity, the ability of FSS to inhibit TNF-α induced apoptosis was significantly decreased. Analysis of anti-apoptotic mechanisms indicated that exposure of MC3T3-E1 cells to FSS for 1 h increased phosphorylation of Bad and inhibited caspase-3 activity. After treatment with XMD8-92, phosphorylation of Bad by FSS was significantly blocked, but caspase-3 activity was increased. In summary, these findings indicated that FSS inhibits TNF-α-mediated signaling events in osteoblast by a mechanism dependent on activation of ERK5, and Bad is a crucial downstream target for ERK5. Those results implied that ERK5 signaling pathway play a crucial role in FSS-mediated anti-apoptotic effect in osteoblast. Thus, ERK5 signaling pathway may be a new drug treatment target of osteoporosis and related bone-wasting diseases.
The Second Hospital of Lanzhou University, #82 Cuiyingmen, Lanzhou 730000, Gansu, China; Orthopaedics Key Laboratory of Gansu Province, Lanzhou 730000, Gansu, China.
Geng
G
Bin
The Second Hospital of Lanzhou University, #82 Cuiyingmen, Lanzhou 730000, Gansu, China; Orthopaedics Key Laboratory of Gansu Province, Lanzhou 730000, Gansu, China.
Wang
W
Cuifang
The Second Hospital of Lanzhou University, #82 Cuiyingmen, Lanzhou 730000, Gansu, China; Orthopaedics Key Laboratory of Gansu Province, Lanzhou 730000, Gansu, China.
Zhang
Z
Bo
The Second Hospital of Lanzhou University, #82 Cuiyingmen, Lanzhou 730000, Gansu, China; Orthopaedics Key Laboratory of Gansu Province, Lanzhou 730000, Gansu, China.
Wang
W
Jing
The Second Hospital of Lanzhou University, #82 Cuiyingmen, Lanzhou 730000, Gansu, China; Orthopaedics Key Laboratory of Gansu Province, Lanzhou 730000, Gansu, China.
Jiang
J
Jin
The Second Hospital of Lanzhou University, #82 Cuiyingmen, Lanzhou 730000, Gansu, China; Orthopaedics Key Laboratory of Gansu Province, Lanzhou 730000, Gansu, China.
Tan
T
Xiaoyi
The Second Hospital of Lanzhou University, #82 Cuiyingmen, Lanzhou 730000, Gansu, China; Orthopaedics Key Laboratory of Gansu Province, Lanzhou 730000, Gansu, China.
Chen
C
Cong
Department of Orthopaedics, the Second Hospital of Lanzhou University, #82 Cuiyingmen, Lanzhou 730000, Gansu, China.
Chen
C
Yonggang
The Second Hospital of Lanzhou University, #82 Cuiyingmen, Lanzhou 730000, Gansu, China; Orthopaedics Key Laboratory of Gansu Province, Lanzhou 730000, Gansu, China.
An
A
Liping
The Second Hospital of Lanzhou University, #82 Cuiyingmen, Lanzhou 730000, Gansu, China; Orthopaedics Key Laboratory of Gansu Province, Lanzhou 730000, Gansu, China.
Ma
M
Jinglin
Department of Orthopaedics, the Second Hospital of Lanzhou University, #82 Cuiyingmen, Lanzhou 730000, Gansu, China. Electronic address: xiayayildey@163.com.
Xia
X
Yayi
D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D051379:Mice; D048054:Mitogen-Activated Protein Kinase 7 / Q000378:metabolism*; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism; D010766:Phosphorylation; D015398:Signal Transduction; D013314:Stress, Mechanical; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D014409:Tumor Necrosis Factor-alpha; D048054:Mitogen-Activated Protein Kinase 7
Apoptosis; Extracellular signal-regulated kinase 5; Fluid shear stress; Osteoblast; TNF-α