Mechanical Strain Inhibits Adipogenesis in Mesenchymal Stem Cells by Stimulating a Durable β-Catenin Signal (original) (raw)

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1Department of Medicine (B.S., Z.X., N.C., M.M., J.R.), University of North Carolina, Chapel Hill, North Carolina 27599

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1Department of Medicine (B.S., Z.X., N.C., M.M., J.R.), University of North Carolina, Chapel Hill, North Carolina 27599

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1Department of Medicine (B.S., Z.X., N.C., M.M., J.R.), University of North Carolina, Chapel Hill, North Carolina 27599

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1Department of Medicine (B.S., Z.X., N.C., M.M., J.R.), University of North Carolina, Chapel Hill, North Carolina 27599

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2Department of Biomedical Engineering (C.R.), State University of New York, Stony Brook, New York 11794

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1Department of Medicine (B.S., Z.X., N.C., M.M., J.R.), University of North Carolina, Chapel Hill, North Carolina 27599

*Address all correspondence and requests for reprints to: Janet Rubin, M.D., 5030 Burnett-Womack, CB No. 7170, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599.

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01 December 2008

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Buer Sen, Zhihui Xie, Natasha Case, Meiyun Ma, Clinton Rubin, Janet Rubin, Mechanical Strain Inhibits Adipogenesis in Mesenchymal Stem Cells by Stimulating a Durable β-Catenin Signal, Endocrinology, Volume 149, Issue 12, 1 December 2008, Pages 6065–6075, https://doi.org/10.1210/en.2008-0687
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The ability of exercise to decrease fat mass and increase bone mass may occur through mechanical biasing of mesenchymal stem cells (MSCs) away from adipogenesis and toward osteoblastogenesis. C3H10T1/2 MSCs cultured in highly adipogenic medium express peroxisome proliferator-activated receptor γ and adiponectin mRNA and protein, and accumulate intracellular lipid. Mechanical strain applied for 6 h daily inhibited expression of peroxisome proliferator-activated receptor γ and adiponectin mRNA by up to 35 and 50%, respectively, after 5 d. A decrease in active and total β-catenin levels during adipogenic differentiation was entirely prevented by daily application of mechanical strain; furthermore, strain induced β-catenin nuclear translocation. Inhibition of glycogen synthase kinase-3β by lithium chloride or SB415286 also prevented adipogenesis, suggesting that preservation of β-catenin levels was important to strain inhibition of adipogenesis. Indeed, mechanical strain inactivated glycogen synthase kinase-3β, which was preceded by Akt activation, indicating that strain transmits antiadipogenic signals through this pathway. Cells grown under adipogenic conditions showed no increase in osteogenic markers runt-related transcription factor (Runx) 2 and osterix (Osx); subsequent addition of bone morphogenetic protein 2 for 2 d increased Runx2 but not Osx expression in unstrained cultures. When cultures were strained for 5 d before bone morphogenetic protein 2 addition, Runx2 mRNA increased more than in unstrained cultures, and Osx expression more than doubled. As such, mechanical strain enhanced MSC potential to enter the osteoblast lineage despite exposure to adipogenic conditions. Our results indicate that MSC commitment to adipogenesis can be suppressed by mechanical signals, allowing other signals to promote osteoblastogenesis. These data suggest that positive effects of exercise on both fat and bone may occur during mesenchymal lineage selection.

Copyright © 2008 by the Endocrine Society

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