文章基本信息

标题：Targeting of the Sonic Hedgehog Pathway by Atractylenolides Promotes Chondrogenic Differentiation of Mesenchymal Stem Cells
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作者：Xican Li ; Gang Wei ; Xiaozhen Wang 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2012
卷号：35
期号：8
页码：1328-1335
DOI：10.1248/bpb.b12-00265
出版社：The Pharmaceutical Society of Japan
摘要：Molecules that enhance chondrogenic differentiation in mesenchymal stem cells (MSCs) were identified and isolated using an in vitro Gli reporter gene assay in MSCs incorporating a Sonic Hedgehog (Shh) target. Atractylenolide III, which promoted Gli1-mediated transcriptional activity, was isolated from an ethyl acetate extract of the Rhizoma, Atractylodis macrocephalae . After dehydration, atractylenolide III was transformed to atractylenolide I. Both atractylenolides were confirmed by MS, UV, IR, ¹H- and ¹³C-NMR spectra. Atractylenolide III (which contains –OH at the 8-position) and atractylenolide I (which lacks –OH at the 8-position) were found to effectively promote the activity of the Gli promoter. While the hydroxyl group of atractylenolide III was not essential for the effect of atractylenolide, its effect was dependent on Shh signaling. Phenotypic cellular analysis indicated that atractylenolides induced MSCs to differentiate into chondrocytes, as shown by increased expression of specific chondrogenic markers including collagen II, aggrecan and the cartilage related transcription factor, Sox9. Atractylenolides significantly increased the expression of Shh and its target gene Gli-1, indicating that Shh signaling was activated by atractylenolides. Moreover, inhibition of Shh signaling reduced the effect of atractylenolides on the chondrogenic phenotype. The discovery that atractylenolides induce chondrocytes from MSCs is promising for bony disease therapy.
关键词：atractylenolide;chondrogenic differentiation;mesenchymal stem cell;sonic hedgehog signaling