Ouattara Amadou, Cooke Diana, Gopalakrishnan Raj, Huang Tsang-Hai, Ables Gene P
Orentreich Foundation for the Advancement of Science, Inc, 855 Route 301, Cold Spring, NY 10516, USA.
School of Dentistry, University of Minnesota, Minneapolis, MN 55455, USA.
Bone Rep. 2016 Feb 11;5:33-42. doi: 10.1016/j.bonr.2016.02.002. eCollection 2016 Dec.
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 , , , and 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.
蛋氨酸限制（MR）可延长多种物种的寿命，包括啮齿动物、果蝇、线虫和酵母。MR也已被证明会影响小鼠和大鼠的整体生长。本研究的目的是评估MR对年轻和老年雄性及雌性C57BL/6J小鼠骨骼结构的影响。该研究表明，MR影响雄性和年轻雌性的生长速度，但不影响老年雌性的生长速度。MR降低了骨体积密度（vBMD）和骨矿物质含量（BMC），与对照喂养（CF）的小鼠相比，雄性和年轻雌性的骨微结构参数降低，但老年雌性没有降低。然而，在根据体重进行调整后，MR在降低vBMD、BMC和微结构测量方面的作用要么减弱，要么逆转，这表明MR小鼠较小的骨骼与其体型相适应。此外，通过纳米压痕测量，CF和MR小鼠具有相似的内在强度特性。血浆生物标志物表明，MR小鼠的低骨量可能是由于胶原降解增加所致，这可能受瘦素、IGF-1、脂联素和FGF21激素水平的影响。在低硫氨基酸生长培养基中培养的小鼠前成骨细胞系减弱了 、 、 、 和 的基因表达水平，表明胶原形成和骨分化延迟。总的来说，我们的研究表明，MR改变了骨形态，这可能是由成骨细胞分化延迟介导的。
