BMP Signaling Mediates Astrocyte Differentiation of Oligodendrocyte Progenitor Cells

BMP Signaling Mediates Astrocyte Differentiation of Oligodendrocyte Progenitor Cells

JIAN-GUO HU,^1,2,3, HE-ZUO LÜ,^1,2 YAN-XIA WANG,⁴ MING-SHENG BAO,³ BAO-MING ZHAO¹ and JIAN-SHENG ZHOU¹

¹Anhui Key Laboratory of Tissue Transplantation, Bengbu Medical College, Bengbu, P.R. China
²Department of Clinical Laboratory Science, The First Affiliated Hospital of Bengbu Medical College, Bengbu, P.R. China
³Department of Cell Biology, Bengbu Medical College, Bengbu, P.R. China
⁴Department of Neurobiology, Shanghai Jiaotong University School of Medicine, Shanghai, P.R. China

Oligodendrocyte precursor cells (OPCs) can differentiate into oligodendrocytes or astrocytes, depending on cellular microenvironments. OPCs, cultured in medium supplemented with 10% (v/v) fetal bovine serum (FBS), give rise to type II astrocytes that express glial fibrillary acidic protein and a cell surface ganglioside that is recognized by A2B5 monoclonal antibody. However, the factors in FBS that direct the astrocyte differentiation are not determined. Moreover, bone morphogenetic proteins (BMPs) have been reported to be involved in astrocyte differentiation of neural progenitor cells. We therefore examined whether BMPs are responsible for the serum-mediated astrocyte differentiation from OPCs. OPCs were isolated from the spinal cords of Wistar rat embryos (at day 14) using the A2B5 antibody. We measured the concentrations of BMP-2 and BMP-4 in FBS and rat and human sera and the expression of mRNAs for three types of BMP receptors (BMPRIa, Ib and II) in OPCs by RT-PCR. The serum samples of the three species contained BMP-2 and BMP-4, as judged by ELISA with each monoclonal antibody, and the BMP receptor mRNAs are expressed in OPCs. When OPCs were cultured in the medium containing 10% FBS, cells (more than 95%) differentiated into type II astrocytes. However, when OPCs were pretreated with noggin, a soluble antagonist of BMP action, the degree of astrocyte differentiation was markedly decreased from 95.39 to 38.36%. Taken together, these results suggest that BMP signaling may be responsible for the serum-mediated astrocyte differentiation of OPCs. Our findings provide new insights into the molecular basis of differentiation of OPCs.

keywords —— Oligodendrocyte progenitor cells; type II astrocytes; differentiation; bone morphogenetic proteins; serum

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Tohoku J. Exp. Med., 2010, 222, 195-200

Correspondence: He-Zuo Lü, Ph.D., Anhui Key Laboratory of Tissue Transplantation, Bengbu Medical College, 287 Chang Huai Road, Bengbu 233004, P.R. China.

e-mail: jghu.hzlv@yahoo.com