Induction of somatopause in adult mice compromises bone morphology and exacerbates bone loss during aging.
Induction of somatopause in adult mice compromises bone morphology and exacerbates bone loss during aging.
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DOI：
10.1111/acel.13505
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发表时间：
2021-12
期刊：
影响因子：
7.8
通讯作者：
Yakar S
中科院分区：
文献类型：
--
作者：
Dixit M;Duran-Ortiz S;Yildirim G;Poudel SB;Louis LD;Bartke A;Schaffler MB;Kopchick JJ;Yakar S
躯体更年期是指生长激素 (GH) 和胰岛素样生长因子-1 在整个衰老过程中逐渐下降。为了确定诱导性体细胞绝经如何影响骨骼完整性，我们使用了诱导性 GH 受体敲除 (iGHRKO) 小鼠模型。在 6 个月大时诱导的体细胞绝经，使雄性和雌性 iGHRKO 小鼠的骨骼明显更细长。在男性中，诱导的躯体更年期与骨髓腔的逐渐扩张有关，导致皮质显着变薄，从而损害骨强度。我们报告称，到 30 个月大时，iGHRKO 男性的骨细胞腔隙数量逐渐减少，腔隙体积增加，而 iGHRKO 女性的腔隙数量减少，并伴有约 20% 的整体小管连接性丧失。诱导的体暂停不影响拉曼显微光谱评估的矿物质/基质比率。我们发现 iGHRKO 小鼠的骨髓脂肪显着增加，硬化蛋白水平升高，硬化蛋白是骨形成的负调节因子。然而，令人惊讶的是，尽管 iGHRKO 小鼠的骨形态受损，但骨细胞衰老却减少了。在这项研究中，我们避免了生长过程中 GH/IGF-1 轴的组成性缺陷对骨骼的混杂影响，并专门剖析了其对衰老骨骼的影响。我们在这里首次表明，诱导的躯体停顿会损害骨形态和骨髓环境。衰老过程中诱发的体细胞停顿会导致 GH/IGF-1 信号下降，抑制桡骨扩张，并与骨髓肥胖增加相关。在骨组织水平上，诱导的体停会导致骨细胞腔隙密度和连接性逐渐下降。
Somatopause refers to the gradual declines in growth hormone (GH) and insulin‐like growth factor‐1 throughout aging. To define how induced somatopause affects skeletal integrity, we used an inducible GH receptor knockout (iGHRKO) mouse model. Somatopause, induced globally at 6 months of age, resulted in significantly more slender bones in both male and female iGHRKO mice. In males, induced somatopause was associated with progressive expansion of the marrow cavity leading to significant thinning of the cortices, which compromised bone strength. We report progressive declines in osteocyte lacunar number, and increases in lacunar volume, in iGHRKO males, and reductions in lacunar number accompanied by ~20% loss of overall canalicular connectivity in iGHRKO females by 30 months of age. Induced somatopause did not affect mineral/matrix ratio assessed by Raman microspectroscopy. We found significant increases in bone marrow adiposity and high levels of sclerostin, a negative regulator of bone formation in iGHRKO mice. Surprisingly, however, despite compromised bone morphology, osteocyte senescence was reduced in the iGHRKO mice. In this study, we avoided the confounded effects of constitutive deficiency in the GH/IGF‐1 axis on the skeleton during growth, and specifically dissected its effects on the aging skeleton. We show here, for the first time, that induced somatopause compromises bone morphology and the bone marrow environment. Induced somatopause during aging causes a drop in GH/IGF‐1 signaling, inhibits radial bone expansion and associates with increased bone marrow adiposity. At the bone tissue level, induced somatopause leads to progressive declines in osteocyte lacunar density and connectivity.
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影响因子：
4.3
作者：
Hemmatian H;Bakker AD;Klein-Nulend J;van Lenthe GH
通讯作者：
van Lenthe GH
DOI：
10.1002/jbmr.2689
发表时间：
2016-02
期刊：
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
影响因子：
--
作者：
Ashpole NM;Herron JC;Mitschelen MC;Farley JA;Logan S;Yan H;Ungvari Z;Hodges EL;Csiszar A;Ikeno Y;Humphrey MB;Sonntag WE
通讯作者：
Sonntag WE
影响因子：
2.4
作者：
Burger, EH;Klein-Nulend, J;Smit, TH
通讯作者：
Smit, TH
影响因子：
3
作者：
Carter, Yasmin;Thomas, C. David L.;Cooper, David M. L.
通讯作者：
Cooper, David M. L.
影响因子：
4.1
作者：
Ding, M;Hvid, I
通讯作者：
Hvid, I