Osteoblast-specific overexpression of amphiregulin leads to transient increase in femoral cancellous bone mass in mice.
Osteoblast-specific overexpression of amphiregulin leads to transient increase in femoral cancellous bone mass in mice.
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成骨细胞特异性过度表达双调蛋白导致小鼠股骨松质骨量短暂增加
DOI：
10.1016/j.bone.2015.06.012
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发表时间：
2015
期刊：
影响因子：
4.1
通讯作者：
Schneider MR
中科院分区：
文献类型：
--
作者：
Vaidya M;Lehner D;Jay FF. Erben RG;Schneider MR
表皮生长因子受体配体双调节蛋白(AREG)参与了骨生理和间歇性甲状旁腺激素治疗所介导的骨合成代谢。然而，AREG在骨骼中的功能仅在体内得到了初步的评估。在这里，我们产生了在成骨细胞中高表达AREG的转基因小鼠(COL1-AREG)。PQCT分析显示，与对照组相比，COL1-ARIG小鼠在4、8和10周龄时股骨干骺端的骨小梁质量增加。然而，高骨量表型是短暂的，在老年动物中消失。对继发性海绵的显微CT分析证实，与对照组相比，4周龄AREG-TG小鼠股骨远端的骨小梁体积和骨小梁数量增加。此外，对原发海绵的μ-CT分析显示，在COL1-ARIG小鼠的股骨远端，新生骨小梁的产生没有改变。组织形态计量学分析显示，在4周大的col1-arg小鼠中，破骨细胞数量减少，但在以后的时间点不再减少。Col1-Areg小鼠的松质骨形成率在所有时间点都保持不变。此外，在研究的所有年龄段，Col1-Areg组和对照组小鼠的腰椎体骨量和骨转换情况相似。从新生小鼠颅骨分离出的成骨细胞的增殖和分化在Col1-Areg组和对照组之间没有差异。综上所述，这些数据表明，AREG在成骨细胞中过表达，通过与生长相关的非细胞自主机制诱导附件骨的小梁室出现一过性的高骨量表型，导致正向骨平衡，骨形成不变，骨吸收降低。
The epidermal growth factor receptor ligand amphiregulin (AREG) has been implicated in bone physiology and in bone anabolism mediated by intermittent parathyroid hormone treatment. However, the functions of AREG in bone have been only incipiently evaluatedin vivo. Here, we generated transgenic mice overexpressing AREG specifically in osteoblasts (Col1-Areg). pQCT analysis of the femoral metaphysis revealed increased trabecular bone mass at 4, 8, and 10 weeks of age in Col1-Areg mice compared to control littermates. However, the high bone mass phenotype was transient and disappeared in older animals. Micro-CT analysis of the secondary spongiosa confirmed increased trabecular bone volume and trabecular number in the distal femur of 4-week-old AREG-tg mice compared to control littermates. Furthermore, μ-CT analysis of the primary spongiosa revealed unaltered production of new bone trabeculae in distal femora of Col1-Areg mice. Histomorphometric analysis revealed a reduced number of osteoclasts in 4-week-old Col1-Areg mice, but not at later time points. Cancellous bone formation rate remained unchanged in Col1-Areg mice at all time points. In addition, bone mass and bone turnover in lumbar vertebral bodies were similar in Col1-Areg and control mice at all ages examined. Proliferation and differentiation of osteoblasts isolated from neonatal calvariae did not differ between Col1-Areg and control mice. Taken together, these data suggest that AREG overexpression in osteoblasts induces a transient high bone mass phenotype in the trabecular compartment of the appendicular skeleton by a growth-related, non-cell autonomous mechanism, leading to a positive bone balance with unchanged bone formation and lowered bone resorption.
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影响因子：
4.1
作者：
Usmani, Shirine E.;Pest, Michael A.;Beier, Frank
通讯作者：
Beier, Frank
骨标记技术
影响因子：
3.7
作者：
R. Erben
通讯作者：
R. Erben
影响因子：
4.8
作者：
Schneider, MR;Dahlhoff, M;Wolf, E
通讯作者：
Wolf, E
影响因子：
10.5
作者：
Fitch, KR;McGowan, KA;Barsh, GS
通讯作者：
Barsh, GS
影响因子：
4.8
作者：
MARTINEAUDOIZE, B;LAI, WH;BERGERON, JJM
通讯作者：
BERGERON, JJM