Inhibition of phosphatidylcholine-specific phospholipase C prevents bone marrow stromal cell senescence in vitro.
Bone marrow stromal cells (BMSCs) can proliferate in vitro and can be transplanted for treating many kinds of diseases. However, BMSCs become senescent with long-term culture, which inhibits their application. To understand the mechanism underlying the senescence, we investigated the activity of phosphatidylcholine-specific phospholipase C (PC-PLC) and levels of integrin beta4, caveolin-1 and ROS with BMSC senescence. The activity of PC-PLC and levels of integrin beta4, caveolin-1 and ROS increased greatly during cell senescence. Selective inhibition of increased PC-PLC activity with D609 significantly decreased the number of senescence-associated beta galactosidase positive cells in BMSCs. Furthermore, D609 restored proliferation of BMSCs and their differentiation into adipocytes. Moreover, D609 suppressed the elevated levels of integrin beta4, caveolin-1 and ROS. The data suggest that PC-PLC is involved in senescence of BMSCs, and its function is associated with integrin beta4, caveolin-1 and ROS.
Sun
Chunhui
C
Institute of Developmental Biology, School of Life Science, Shandong University, Jinan 250100, China.
Wang
Nan
N
Huang
Jie
J
Xin
Jie
J
Peng
Fen
F
Ren
Yinshi
Y
Zhang
Shangli
S
Miao
Junying
J
D050156:Adipogenesis; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D051242:Caveolin 1 / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D016922:Cellular Senescence; D039663:Integrin beta4 / Q000378:metabolism; D008297:Male; D010713:Phosphatidylcholines / Q000378:metabolism*; D021381:Protein Transport; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D017154:Stromal Cells / Q000378:metabolism* / Q000473:pathology; D013379:Substrate Specificity; D013997:Time Factors; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D001616:beta-Galactosidase / Q000378:metabolism
D051242:Caveolin 1; D039663:Integrin beta4; D010713:Phosphatidylcholines; D017382:Reactive Oxygen Species; D010738:Type C Phospholipases; D001616:beta-Galactosidase; D002118:Calcium