Cholesterol myristate suppresses the apoptosis of mesenchymal stem cells via upregulation of inhibitor of differentiation.
To identify small molecules that suppress the apoptosis of mesenchymal stem cells (MSCs) is promising for stem cell therapy. We recently showed that bone morphogenetic protein 4 (BMP4) signalling involves the effect of cholesterol myristate on the proliferation of MSCs. The present study evaluated the effects of cholesterol myristate on the apoptosis of MSCs and the inhibitor of differentiation (Id1), target gene of BMP4 signalling. MSCs transfected by the Id1 promoter reporter construct, cholesterol myristate increases the activity of Id1 promoter. However, structurally related steroids such as cholesterol, β-sitosterol and cholesten-3-one, lack of the myristate, did not affect the activity of Id1 promoter, suggesting that myristate is essential for this effect. This effect depends on BMP signalling. Apoptosis analysis indicated that cholesterol myristate inhibited the apoptosis of MSCs induced by serum-free. Cholesterol myristate increases the expression of Id1 and its target gene bcl-x/l in MSCs treated with serum-free. Moreover, noggin, a BMP antagonist, reduced the anti-apoptotic effects of cholesterol myristate. Thus, this study aims to provide evidence that cholesterol myristate suppresses the apoptosis of MSCs via up-regulation of Id1. These findings can be applied for improving MSCs survival in stem-cell transplantation, bone-marrow transplantation, treatment of bone diseases such as osteoporosis and chemotherapy.
Chen
Dong-Feng
DF
The State Key Laboratory of Pharmaceutical Biotechnology, Department of Biochemistry, Nanjing University, Nanjing, China. CDF27212@21cn.com
Zhang
Hai-Ling
HL
Du
Shao-Hui
SH
Li
Hui
H
Zhou
Jian-Hong
JH
Li
Yi-Wei
YW
Zeng
He-Ping
HP
Hua
Zi-Chun
ZC
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002352:Carrier Proteins / Q000494:pharmacology; D002788:Cholesterol Esters / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D016895:Culture Media, Serum-Free / Q000378:metabolism; D017930:Genes, Reporter / Q000235:genetics; D051796:Inhibitor of Differentiation Proteins / Q000235:genetics* / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D014162:Transfection; D015854:Up-Regulation / Q000187:drug effects*; D000099176:Noggin Protein
D002352:Carrier Proteins; D002788:Cholesterol Esters; D016895:Culture Media, Serum-Free; D051796:Inhibitor of Differentiation Proteins; D000099176:Noggin Protein; C032561:cholesteryl myristate