Asiatic acid inhibits adipogenic differentiation of bone marrow stromal cells.
Bone marrow mesenchymal stromal cells (BMSCs) are the common precursors for both osteoblasts and adipocytes. With aging, BMSC osteoblast differentiation decreases whereas BMSC differentiation into adipocytes increases, resulting in increased adipogenesis and bone loss. In the present study, we investigated the effect of asiatic acid (AA) on adipocytic differentiation of BMSCs. AA inhibited the adipogenic induction of lipid accumulation, activity of glycerol-3-phosphate dehydrogenase, and expression of marker genes in adipogenesis: peroxisome proliferation-activated receptor (PPAR)γ, adipocyte fatty acid-binding protein (ap) 2, and adipsin. Further, we found that AA did not alter clonal expansion rate and expression of C/EBPβ, upstream key regulator of PPARγ, and binding activity of C/EBPβ to PPARγ promoter was not affected by AA as well. These findings suggest that AA may modulate differentiation of BMSCs to cause a lineage shift away from the adipocytes, and inhibition of PPARγ by AA is through C/EBPβ-independent mechanisms. Thus, AA could be a potential candidate for a novel drug against osteoporosis.
The Second Clinical Hospital of JiLin University, Changchun, 130041, People's Republic of China.
Zheng-Wei
ZW
Li
Cheng-dong
CD
Piao
Hong-hui
HH
Sun
Xian-Sheng
XS
Ren
Yun-Shen
YS
Bai
D050156:Adipogenesis / Q000187:drug effects; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D011416:Complement Factor D / Q000378:metabolism; D050556:Fatty Acid-Binding Proteins / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D053978:Pentacyclic Triterpenes / Q000494:pharmacology*; D011401:Promoter Regions, Genetic
D022782:CCAAT-Enhancer-Binding Protein-beta; C545013:Cebpb protein, mouse; C493411:Fabp4 protein, mouse; D050556:Fatty Acid-Binding Proteins; D047495:PPAR gamma; D053978:Pentacyclic Triterpenes; C017032:asiatic acid; D011416:Complement Factor D