Mechanical Stimulation of Mesenchymal Stem Cell Proliferation and Differentiation Promotes Osteogenesis While Preventing Dietary-Induced Obesity

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 marrowbased 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 PPAR␥ 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 fraction in the tibia was increased by 11%. Translating this to the clinic, a 1-yr trial in young women (15-20 yr; n ‫ס‬ 48) with osteopenia showed that LMMS increased trabecular bone in the spine and kept visceral fat at baseline levels, whereas control subjects showed no change in BMD, yet an increase in visceral fat. Mechanical modulation of stem cell proliferation and differentiation indicates a unique therapeutic target to aid in tissue regeneration and repair and may represent the basis of a nonpharmacologic strategy to simultaneously prevent obesity and osteoporosis.

In vivo anabolic effect of strontium on trabecular bone was associated with increased osteoblastogenesis of bone marrow stromal cells

“…Furthermore, several agents or stimuli exert the anabolic effect with this mechanism. 2,3,26 In the current study, the greater bone volume after Sr treatment was accompanied with an increased osteogenic and decreased adipogenic potential of BMSCs by ex vivo study. Considering that Sr can increase osteogenic differentiation of murine or human BMSCs in vitro, 11,12 the in vivo anabolic effect of Sr may at least partially be attributed to the favorable differentiation of osteoblast lineage.…”

“…Recent studies suggest that low magnitude mechanical signals can increase bone volume and reduce fat tissues in male mice by stimulating BMSCs proliferation and differentiation into an osteoblast lineage. 2 Moreover, Bortezomib (Bzb), a first-in-class proteasome inhibitor used to treat myeloma patients, exerts an anabolic effect on bone by stimulating the differentiation of BMSCs into osteoblasts, thus leading to new bone formation. 3 These studies indicate that modulation of in vivo lineage differentiation of BMSCs is a feasible approach to build bone volume, which may serve as a new strategy to treat postmenopausal osteoporosis.…”

Diet vs exercise for the prevention of pediatric obesity: the role of exercise

“…Although these studies have generally been conducted in rodent models, some confirming human data are becoming available. 18 The mechanical stimulation imparted by the vibrating platforms used in these studies has been of very low magnitude, which would seem to argue against the vigorous PA hypothesis. However, the frequency of the stimulation has been relatively high.…”

Gene Expression Responses to Mechanical Stimulation of Mesenchymal Stem Cells Seeded on Calcium Phosphate Cement

“…Further, a number of studies in vivo have been carried out in an attempt to overcome these obstacles, but these are limited to animal models and therefore could be associated with differences in responses to loading and mechanisms involved from one species to another. 21,22 In addition, the presence of a mixed population of cells within these settings makes it difficult to study responses from specific cell types such as osteoblasts or mesenchymal stem cells (MSC).…”