Mechanical stimulation of mesenchymal stem cell proliferation and differentiation promotes osteogenesis while preventing dietary-induced obesity.

Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research
Yen Kim LuuC T Rubin

Abstract

Mesenchymal stem cells (MSCs) are defined by their ability to self-renew and differentiate into the cells that form mesodermal tissues such as bone and fat. Low magnitude mechanical signals (LMMS) have been shown to be anabolic to bone and have been recently reported to suppress the development of fat in normal animals fed a regular diet. Using male C57BL/6J mice, the ability of LMMS (0.2g, 90-Hz signal applied for 15 min/d, 5 d/wk) to simultaneously promote bone formation and prevent diet-induced obesity was correlated to mechanical influences on the molecular environment of the bone marrow, as indicated by the population dynamics and lineage commitment of MSCs. Six weeks of LMMS increased the overall marrow-based stem cell population by 37% and the number of MSCs by 46%. Concomitant with the increase in stem cell number, the differentiation potential of MSCs in the bone marrow was biased toward osteoblastic and against adipogenic differentiation, as reflected by upregulation of the transcription factor Runx2 by 72% and downregulation of PPARgamma by 27%. The phenotypic impact of LMMS on MSC lineage determination was evident at 14 wk, where visceral adipose tissue formation was suppressed by 28%, whereas trabecular bone volume...Continue Reading

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