Methionine restriction alters bone morphology and affects osteoblast differentiation

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.

Dietary methionine restriction modulates renal response and attenuates kidney injury in mice

“…Plasma markers for renal injury—for example, A2M, cystatin C, lipocalin 2, and clusterin—were reduced (Table 3; P < 0.05) in 5/6Nx MR mice compared with 5/6Nx CF mice. Consistent with other studies on MR mice (14, 17), 5/6Nx MR mice exhibited less weight gain than did 5/6Nx CF mice (Supplemental Fig. 2 C ; P < 0.001), despite increased food intake (Supplemental Fig.…”

“…We also measured known plasma markers that are affected by MR (Supplemental Table 3). Current data are consistent with our previous studies (14,17) in that FGF-21 and adiponectin were significantly elevated (P , 0.01 and P , 0.001, respectively), whereas IGF-1 and leptin levels were significantly reduced (P , 0.05 and P , 0.01, respectively) in UNx MR mice compared with UNx CF mice. Renal gene expression for selected ion transporter genes indicated upregulation of the markers, Aqp2, Slc12a1, Scnn1a, Slc26a4, and Slc6a19, in UNx MR mice compared with UNx CF mice ( Fig.…”

Short term methionine restriction increases hepatic global DNA methylation in adult but not young male C57BL/6J mice

“…Effects of MR on growth rates and food intake in both young and adult mice were similar to those previously observed in rodents [20]. Young mice on the CD continued to grow until the end of the study; those on MR also continued to grow but at a slower rate (Figure 1).…”

Dietary restrictions, bone density, and bone quality

“…In the nano‐indentation measurements performed on the surfaces of vertebrate bodies, ovariectomized rats that were fed a PR‐diet exhibited a lower tissue elastic modulus, hardness, and energy dissipation compared to those of the sham group, and a 5% essential amino acid supplement reversed this loss in intrinsic strength . However, under isoprotein conditions, our research team found that specific restrictions in dietary methionine did not change the intrinsic material properties that were measured by nano‐indentation in young and adult mice of both genders (Ouattara et al ., unpublished) . More studies that use this novel material testing system to explore the effects of dietary restrictions on the skeleton are definitely required.…”

“…147 However, under isoprotein conditions, our research team found that specific restrictions in dietary methionine did not change the intrinsic material properties that were measured by nano-indentation in young and adult mice of both genders (Ouattara et al, unpublished). 148 More studies that use this novel material testing system to explore the effects of dietary restrictions on the skeleton are definitely required.…”