Cyclic Compressive Stress Regulates Apoptosis in Rat Osteoblasts: Involvement of PI3K/Akt and JNK MAPK Signaling Pathways.
It is widely accepted that physiological mechanical stimulation suppresses apoptosis and induces synthesis of extracellular matrix by osteoblasts; however, the effect of stress overloading on osteoblasts has not been fully illustrated. In the present study, we investigated the effect of cyclic compressive stress on rat osteoblasts apoptosis, using a novel liquid drop method to generate mechanical stress on osteoblast monolayers. After treatment with different levels of mechanical stress, apoptosis of osteoblasts and activations of mitogen-activated protein kinases (MAPKs) and PI3-kinase (PI3K)/Akt signaling pathways were investigated. Osteoblasts apoptosis was observed after treated with specific inhibitors prior to mechanical stimulation. Protein levels of Bax/Bcl-2/caspase-3 signaling were determined using western blot with or without inhibitors of PI3K/Akt and phosphorylation of c-jun N-terminal kinase (JNK) MAPK. Results showed that mechanical stimulation led to osteoblasts apoptosis in a dose-dependent manner and a remarkable activation of MAPKs and PI3K/Akt signaling pathways. Activation of PI3K/Akt protected against apoptosis, whereas JNK MAPK increased apoptosis via regulation of Bax/Bcl-2/caspase-3 activation. In summary, the PI3K/Akt and JNK MAPK signaling pathways played opposing roles in osteoblasts apoptosis, resulting in inhibition of apoptosis upon small-magnitude stress and increased apoptosis upon large-magnitude stress.
Department of Orthopedics, Third Affiliated Hospital of PLA Second Military Medical University, Shanghai, 200433, China.
Fanglong
F
Song
Department of Orthopedics, Third Affiliated Hospital of PLA Second Military Medical University, Shanghai, 200433, China.
Yi
Y
Wang
Department of Orthopedics, Third Affiliated Hospital of PLA Second Military Medical University, Shanghai, 200433, China.
Dawei
D
Jiang
Department of Orthopedics, Third Affiliated Hospital of PLA Second Military Medical University, Shanghai, 200433, China.
Tianchen
T
Wang
Department of Orthopedics, Third Affiliated Hospital of PLA Second Military Medical University, Shanghai, 200433, China.
Yinquan
Y
Zhang
Department of Orthopedics, Third Affiliated Hospital of PLA Second Military Medical University, Shanghai, 200433, China.
Hui
H
Ma
Department of Orthopedics, Third Affiliated Hospital of PLA Second Military Medical University, Shanghai, 200433, China.
Yifan
http://orcid.org/0000-0002-5856-6643
Y
Kang
D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism*; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D002470:Cell Survival; D020935:MAP Kinase Signaling System; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D013314:Stress, Mechanical
D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; C505410:Casp3 protein, rat; D053148:Caspase 3