Abstract
Methionine restriction (MR) extends the lifespan of a wide variety of species, including rodents, drosophila, nematodes, and yeasts. MR has also been demonstrated to affect the overall growth of mice and rats. The objective of this study was to evaluate the effect of MR on bone structure in young and aged male and female C57BL/6J mice. This study indicated that MR affected the growth rates of males and young females, but not aged females. MR reduced volumetric bone mass density (vBMD) and bone mineral content (BMC), while bone microarchitecture parameters were decreased in males and young females, but not in aged females compared to control-fed (CF) mice. However, when adjusted for bodyweight, the effect of MR in reducing vBMD, BMC and microarchitecture measurements was either attenuated or reversed suggesting that the smaller bones in MR mice is appropriate for its body size. In addition, CF and MR mice had similar intrinsic strength properties as measured by nanoindentation. Plasma biomarkers suggested that the low bone mass in MR mice could be due to increased collagen degradation, which may be influenced by leptin, IGF-1, adiponectin and FGF21 hormone levels. Mouse preosteoblast cell line cultured under low sulfur amino acid growth media attenuated gene expression levels of Col1al, Runx2, Bglap, Alpl and Spp1 suggesting delayed collagen formation and bone differentiation. Collectively, our studies revealed that MR altered bone morphology which could be mediated by delays in osteoblast differentiation.
Highlights
Methionine restriction (MR) extends the lifespan of a wide variety of species, including rodents, drosophila, nematodes, and yeasts (BrownBorg et al, 2014; Cabreiro et al, 2013; Johnson and Johnson, 2014; Lee et al, 2014; Miller et al, 2005; Orentreich et al, 1993; Richie et al, 1994; Ruckenstuhl et al, 2014)
We previously reported that mice provided a high-fat methionine-restricted diet (HFD-MR) exhibited growth restriction compared to their high-fat diet (HFD)-CF counterparts, which could be due to increased collagen degradation (Ables et al, 2012)
We examined whether volumetric bone mass density (vBMD) and bone mineral content (BMC) were affected by MR
Summary
Methionine restriction (MR) extends the lifespan of a wide variety of species, including rodents, drosophila, nematodes, and yeasts (BrownBorg et al, 2014; Cabreiro et al, 2013; Johnson and Johnson, 2014; Lee et al, 2014; Miller et al, 2005; Orentreich et al, 1993; Richie et al, 1994; Ruckenstuhl et al, 2014). Huang et al reported that MR rats were smaller; had reduced bone mass compared to CF rats, as determined by microcomputed tomography (μCT); and had decreased extrinsic strength, as measured by a 3-point bending test (Huang et al, 2014). Bones from MR rats had higher intrinsic biomaterial strength and toughness compared to CF rats (Huang et al, 2014). These studies suggest that MR affects overall bone development in rodents
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