The differential effects of aligned electrospun PHBHHx fibers on adipogenic and osteogenic potential of MSCs through the regulation of PPARγ signaling.
Cell-substrate interaction was functionally essential for phenotypic maintenance and multipotency remodeling of stem cells. For bone tissue engineering, electrospinning techniques are useful to create fibrous scaffolds mimicking natural mineralized collagen fibrous structure in bone. In this study, influence of electrospun fiber alignment on MSCs differentiation potential was investigated on PHBHHx electrospun meshes. Compared with randomly-oriented ones, the aligned fiber orientation increased elastic modulus and tension stress of the PHBHHx meshes. Most of the attached MSCs elongated along the aligned fibers. From the transcriptome microarray results, there were a total of 67 differentially expressed genes between aligned and random groups, and most of them were involved in cell adhesion and actin cytoskeleton regulation. In addition, PPAR signaling pathway was reduced on the aligned fibers, which might contribute to the impaired adipogenesis and enhanced osteogenesis. It was further confirmed by RT-PCR and western blotting. The PPARγ downregulation on the aligned fibers was related to phosphorylated activation of ERK, with no effect on total ERK expression. However, the induction of osteogenic by PHBHHx fiber alignment was relatively less significant that it could only support initial adipo-osteogenic switch and would be partially covered up by osteogenic or adipogenic inductive chemicals.
Ministry of Education Key Laboratory of Bioinformatics, School of Life Sciences, Tsinghua University, Beijing 100084, China.
Yang
Y
Wang
Rui
R
Gao
Pei-Pei
PP
Wang
Jia
J
Jian
Xian-Li
XL
Jiang
Chao
C
Yan
Xiao
X
Lin
Li
L
Wu
Guo-Qiang
GQ
Chen
Qiong
Q
Wu
D020155:3-Hydroxybutyric Acid / Q000737:chemistry*; D050156:Adipogenesis / Q000187:drug effects*; D000818:Animals; D002208:Caproates / Q000737:chemistry*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D015536:Down-Regulation; D020869:Gene Expression Profiling; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D046228:Microarray Analysis; D008855:Microscopy, Electron, Scanning; D010012:Osteogenesis / Q000187:drug effects*; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D023822:Tissue Engineering / Q000379:methods; D059467:Transcriptome; D000094122:Polyhydroxybutyrates
D020155:3-Hydroxybutyric Acid; D002208:Caproates; D047495:PPAR gamma; C115940:poly(3-hydroxybutyrate-co-3-hydroxyhexanoate); D000094122:Polyhydroxybutyrates