Deletion of the nuclear localization sequence and C-terminus of parathyroid hormone-related protein decreases osteogenesis and chondrogenesis but increases adipogenesis and myogenesis in murine bone marrow stromal cells.
Deletion of the nuclear localization sequence and C-terminus of parathyroid hormone-related protein decreases osteogenesis and chondrogenesis but increases adipogenesis and myogenesis in murine bone marrow stromal cells.
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甲状旁腺激素相关蛋白的核定位序列和C末端的缺失减少了成骨和软骨发生，但增加了鼠骨髓基质细胞中的脂肪形成和肌发生。
DOI：
10.1177/2041731415609298
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发表时间：
2015-01
影响因子：
8.2
通讯作者：
Toribio RE
中科院分区：
文献类型：
--
作者：
Hildreth BE 3rd;Hernon KM;Dirksen WP;Leong J;Supsavhad W;Boyaka PN;Rosol TJ;Toribio RE
甲状旁腺相关蛋白N端调控骨髓基质细胞分化我们推测，核定位序列和C-末端参与。对来自缺乏核定位序列和C末端（PthrpΔ/Δ）的小鼠和年龄匹配的对照的骨髓基质细胞进行microRNA和基因表达分析。进行分化测定，包括microRNA、细胞化学/组织学/形态学、蛋白质和基因表达分析。PthrpΔ/Δ骨髓基质细胞具有抗骨软骨生成、促脂肪生成和促肌生成作用，表达更多的Klf 4、Gsk-3β、Lif、Ct-1和microRNA-434，但表达较少的β-连环蛋白、Igf-1、Taz、Osm和microRNA-22（p <0.024）。PthrpΔ/Δ成骨细胞的矿化、骨钙素、Runx 2、Osx、IGF-1和瘦素较少（p <0.029）。PthrpΔ/Δ产生更多的脂肪细胞、Pparγ和aP 2，但更少的Lpl（p <0.042）。PthrpΔ/Δ软骨颗粒较小，Sox 9和Pth 1 r较少，但Col 2a 1较大（p <0.024）。PthrpΔ/Δ产生更多的肌细胞、Des和Myog（p <0.021）。microRNA的变化支持了这些发现。总之，核定位序列和C-末端是促骨软骨形成、抗脂肪形成和抗肌形成的。
The N-terminus of parathyroid hormone–related protein regulates bone marrow stromal cell differentiation. We hypothesized that the nuclear localization sequence and C-terminus are involved. MicroRNA and gene expression analyses were performed on bone marrow stromal cells from mice lacking the nuclear localization sequence and C-terminus (PthrpΔ/Δ) and age-matched controls. Differentiation assays with microRNA, cytochemical/histologic/morphologic, protein, and gene expression analyses were performed. PthrpΔ/Δ bone marrow stromal cells are anti-osteochondrogenic, pro-adipogenic, and pro-myogenic, expressing more Klf4, Gsk-3β, Lif, Ct-1, and microRNA-434 but less β-catenin, Igf-1, Taz, Osm, and microRNA-22 (p ⩽ 0.024). PthrpΔ/Δ osteoblasts had less mineralization, osteocalcin, Runx2, Osx, Igf-1, and leptin (p ⩽ 0.029). PthrpΔ/Δ produced more adipocytes, Pparγ, and aP2, but less Lpl (p ⩽ 0.042). PthrpΔ/Δ cartilage pellets were smaller with less Sox9 and Pth1r, but greater Col2a1 (p ⩽ 0.024). PthrpΔ/Δ produced more myocytes, Des, and Myog (p ⩽ 0.021). MicroRNA changes supported these findings. In conclusion, the nuclear localization sequence and C-terminus are pro-osteochondrogenic, anti-adipogenic, and anti-myogenic.
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影响因子：
3.7
作者：
Garzia L;Andolfo I;Cusanelli E;Marino N;Petrosino G;De Martino D;Esposito V;Galeone A;Navas L;Esposito S;Gargiulo S;Fattet S;Donofrio V;Cinalli G;Brunetti A;Vecchio LD;Northcott PA;Delattre O;Taylor MD;Iolascon A;Zollo M
通讯作者：
Zollo M
DOI：
10.1016/j.jss.2010.02.023
发表时间：
2010-08
期刊：
The Journal of surgical research
影响因子：
--
作者：
Hildreth BE 3rd;Werbeck JL;Thudi NK;Deng X;Rosol TJ;Toribio RE
通讯作者：
Toribio RE
影响因子：
4
作者：
Huang, Shan;Wang, Shihua;Zhao, Robert Chunhua
通讯作者：
Zhao, Robert Chunhua
影响因子：
--
作者：
Chou, Wen-Wen;Wang, Yu-Ting;Juo, Suh-Hang Hank
通讯作者：
Juo, Suh-Hang Hank
影响因子：
4.8
作者：
Chan, GK;Miao, DS;Goltzman, D
通讯作者：
Goltzman, D