Autocrine BMP4 signaling involves effect of cholesterol myristate on proliferation of mesenchymal stem cells.
We recently identified that cholesterol myristate in traditional Chinese medicine (TCM) is the active compound that increases proliferation of mesenchymal stem cell (MSCs). The present study is further to determine what signal pathway involves in effect of cholesterol myristate. Reverse transcription-PCR, Western blot and ELISA analysis show that cholesterol myristate increases the release of bone morphogenetic protein 4 (BMP4) from MSCs and the expression in the intracellular levels of BMP4 in a time- and dose dependent manner. However, structurally related steroids such as cholesterol and cholesten presented in TCM, both lack of the myristate, did not affect the secretion and expression of BMP4 on MSCs. These finds suggest that myristate is essential for the effects of cholesterol myristate. Furthermore, cholesterol myristate significantly increase BMPRIB levels of MSCs and the number of BMPRIB positive cells in a time- and dose dependent manner, but not BMPR IA or BMPR II. Our results indicate that action of cholesterol myristate may activate the BMP4-BMPRIB autocrine. Moreover, a blocking antibody against BMP4 or the BMP4 antagonist, noggin, partially reduced the effects of cholesterol myristate on MSCs proliferation. Thus, this study is to provide evidence that autocrine BMP4 signaling involves effect of cholesterol myristate on MSCs proliferation.
Chen
Dong-Feng
DF
Department of Anatomy, Guangzhou University of Traditional Chinese Medicine, No. 12 Jichang Road, Guangzhou, China. CDF27212@21cn.com
Du
Shao-Hui
SH
Zhang
Hai-Ling
HL
Li
Hui
H
Zhou
Jian-Hong
JH
Li
Yi-Wei
YW
Yi
Xiang-Hua
XH
Hou
Qiu-Ke
QK
Wu
Jing
J
Zeng
He-Ping
HP
Hua
Zi-Chun
ZC
D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D019898:Autocrine Communication / Q000187:drug effects* / Q000502:physiology; D055415:Bone Morphogenetic Protein 4 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000819:agonists / Q000378:metabolism*; D002352:Carrier Proteins / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects*; D002788:Cholesterol Esters / Q000494:pharmacology*; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D000099176:Noggin Protein
D057134:Antibodies, Neutralizing; D055415:Bone Morphogenetic Protein 4; D052005:Bone Morphogenetic Protein Receptors, Type I; D002352:Carrier Proteins; D002788:Cholesterol Esters; D000099176:Noggin Protein; C032561:cholesteryl myristate