Impaired osteoblast and osteoclast function characterize the osteoporosis of Snyder - Robinson syndrome.
Impaired osteoblast and osteoclast function characterize the osteoporosis of Snyder - Robinson syndrome.
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成骨细胞和破骨细胞功能受损，表征了斯奈德 - 鲁滨逊综合征的骨质疏松症。
DOI：
10.1186/s13023-015-0235-8
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发表时间：
2015-03-07
影响因子：
3.7
通讯作者：
Boerkoel CF
中科院分区：
文献类型：
--
作者：
Albert JS;Bhattacharyya N;Wolfe LA;Bone WP;Maduro V;Accardi J;Adams DR;Schwartz CE;Norris J;Wood T;Gafni RI;Collins MT;Tosi LL;Markello TC;Gahl WA;Boerkoel CF
Snyder-Robinson Syndrome (SRS) is an X-linked intellectual disability disorder also characterized by osteoporosis, scoliosis, and dysmorphic facial features. It is caused by mutations in SMS, a ubiquitously expressed gene encoding the polyamine biosynthetic enzyme spermine synthase. We hypothesized that the tissue specificity of SRS arises from differential sensitivity to spermidine toxicity or spermine deficiency. We performed detailed clinical, endocrine, histopathologic, and morphometric studies on two affected brothers with a spermine synthase loss of function mutation (NM_004595.4:c.443A > G, p.Gln148Arg). We also measured spermine and spermidine levels in cultured human bone marrow stromal cells (hBMSCs) and fibroblasts using the Biochrom 30 polyamine protocol and assessed the osteogenic potential of hBMSCs. In addition to the known tissue-specific features of SRS, the propositi manifested retinal pigmentary changes, recurrent episodes of hyper- and hypoglycemia, nephrocalcinosis, renal cysts, and frequent respiratory infections. Bone histopathology and morphometry identified a profound depletion of osteoblasts and osteoclasts, absence of a trabecular meshwork, a low bone volume and a thin cortex. Comparison of cultured fibroblasts from affected and unaffected individuals showed relatively small changes in polyamine content, whereas comparison of cultured osteoblasts identified marked differences in spermidine and spermine content. Osteogenic differentiation of the SRS-derived hBMSCs identified a severe deficiency of calcium phosphate mineralization. Our findings support the hypothesis that cell specific alterations in polyamine metabolism contribute to the tissue specificity of SRS features, and that the low bone density arises from a failure of mineralization. The online version of this article (doi:10.1186/s13023-015-0235-8) contains supplementary material, which is available to authorized users.
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DOI：
10.1073/pnas.89.22.10915
发表时间：
1992-11-15
影响因子：
11.1
作者：
HENIKOFF, S;HENIKOFF, JG
通讯作者：
HENIKOFF, JG
影响因子：
4.8
作者：
Kondo, H;Nifuji, A;Noda, M
通讯作者：
Noda, M
影响因子：
14.8
作者：
Kumar, Prateek;Henikoff, Steven;Ng, Pauline C.
通讯作者：
Ng, Pauline C.
影响因子：
2
作者：
Manoli, Irini;Golas, Gretchen;Westbroek, Wendy;Vilboux, Thierry;Markello, Thomas C.;Introne, Wendy;Maynard, Dawn;Pederson, Ben;Tsilou, Ekaterini;Jordan, Michael B.;Hart, P. Suzanne;White, James G.;Gahl, William A.;Huizing, Marjan
通讯作者：
Huizing, Marjan
DOI：
10.1084/jem.20102608
发表时间：
2011-04-11
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Kajimura D;Hinoi E;Ferron M;Kode A;Riley KJ;Zhou B;Guo XE;Karsenty G
通讯作者：
Karsenty G