Mechanical stretch inhibits mesenchymal stem cell adipogenic differentiation through TGFβ1/Smad2 signaling.
Mesenchymal stem cells (MSCs) are the common precursors of several functionally disparate cell lineages. A plethora of chemical and physical stimuli contribute to lineage decisions and guidance, including mechanical stretch concomitant with physical movement. Here, we examined how stretch regulates MSC differentiation into adipocytes and the intracellular signaling pathways involved. MSCs were cultured under adipogenic conditions and divided into a control and an experimental group. Cultures in the experimental group were subjected to a sinusoidal stretch regimen delivered via flexible culture bottoms (5% magnitude, 10 times per min, 6h/day, 3 or 5 days). Expression levels of the adipocyte markers PPARγ-2, adiponectin, and C/EBPα were measured as indices of differentiation. Compared to controls, MSCs exposed to mechanical stretch exhibited downregulated PPARγ-2, adiponectin, and C/EBPα mRNA expression. Alternatively, stretch upregulated phosphorylation of Smad2. This stretch-induced increase in Smad2 phosphorylation was suppressed by pretreatment with the TGFβ1/Smad2 pathway antagonist SB-431542. Pretreatment with the TGFβ1/Smad2 signaling agonist TGFβ1 facilitated the inhibitory effect of stretch on the expression levels of PPARγ-2, adiponectin, and C/EBPα proteins, while pretreatment with SB-431542 reversed the inhibitory effects of subsequent stretch on the expression levels of these markers. These results strongly suggest that the anti-adipogenic effects of mechanical stretch on MSCs are mediated, at least in part, by activation of the TGFβ1/Smad2 signaling pathway.
Department of Orthopedics and Traumatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China; Huiqiao Department, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China; Key Laboratory of Bone and Cartilage Regenerative Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
Runguang
R
Li
Department of Orthopedics and Traumatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China; Key Laboratory of Bone and Cartilage Regenerative Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
Liang
L
Liang
Department of Orthopedics and Traumatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China; Key Laboratory of Bone and Cartilage Regenerative Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
Yonggang
Y
Dou
Department of Orthopedics and Traumatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China; Key Laboratory of Bone and Cartilage Regenerative Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
Zeping
Z
Huang
Department of Orthopedics and Traumatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China; Key Laboratory of Bone and Cartilage Regenerative Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
Huiting
H
Mo
Department of Orthopedics and Traumatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China; Key Laboratory of Bone and Cartilage Regenerative Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
Yaning
Y
Wang
Department of Orthopedics and Traumatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China; Key Laboratory of Bone and Cartilage Regenerative Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. Electronic address: yubincsgk@163.com.
Bin
B
Yu
D017667:Adipocytes / Q000166:cytology; D050156:Adipogenesis; D052242:Adiponectin / Q000378:metabolism; D000818:Animals; D001549:Benzamides; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D004149:Dioxoles; D015536:Down-Regulation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology*; D047495:PPAR gamma / Q000378:metabolism; D010766:Phosphorylation; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D051899:Smad2 Protein / Q000378:metabolism*; D013314:Stress, Mechanical; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
C459179:4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide; D052242:Adiponectin; D001549:Benzamides; D022763:CCAAT-Enhancer-Binding Protein-alpha; D004149:Dioxoles; D047495:PPAR gamma; D051899:Smad2 Protein; C497784:Smad2 protein, rat; C508962:Tgfb1 protein, rat; D053773:Transforming Growth Factor beta1
Adipogenic differentiation; Mesenchymal stem cell; Smad2; Stretch; TGFβ1