title: Inhibition of phosphatidylcholine-specific phospholipase C prevents bone marrow stromal cell senescence in vitro.
abstract: 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.
authors.affiliation: Institute of Developmental Biology, School of Life Science, Shandong University, Jinan 250100, China.
authors.forename: Chunhui
authors.initials: C
authors.lastname: Sun
authors.forename: Nan
authors.initials: N
authors.lastname: Wang
authors.forename: Jie
authors.initials: J
authors.lastname: Huang
authors.forename: Jie
authors.initials: J
authors.lastname: Xin
authors.forename: Fen
authors.initials: F
authors.lastname: Peng
authors.forename: Yinshi
authors.initials: Y
authors.lastname: Ren
authors.forename: Shangli
authors.initials: S
authors.lastname: Zhang
authors.forename: Junying
authors.initials: J
authors.lastname: Miao
mesh_terms: 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
chemical_list: D051242:Caveolin 1; D039663:Integrin beta4; D010713:Phosphatidylcholines; D017382:Reactive Oxygen Species; D010738:Type C Phospholipases; D001616:beta-Galactosidase; D002118:Calcium