JunD suppresses bone formation and contributes to low bone mass induced by estrogen depletion
JunD suppresses bone formation and contributes to low bone mass induced by estrogen depletion
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DOI：
10.1002/jcb.21660
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发表时间：
2008-03-01
影响因子：
4
通讯作者：
Noda, Masaki
中科院分区：
文献类型：
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作者：
Kawamata, Aya;Izu, Yayoi;Noda, Masaki
Jund是一种激活蛋白-1(AP-1)，但其在骨骼系统中的功能尚不完全清楚。为了阐明Jund在骨代谢调节中的作用，我们分析了Jund缺陷小鼠。正虚组大鼠骨量明显增加，骨小梁数目明显增加。这种骨量增加是由于延髓缺乏诱导体内骨形成活性的增加。这种骨形成的增强与骨吸收的同时增加有关，而前者比后者占优势，因为在Jund缺陷小鼠中发生了骨量积累。在一种与绝经后骨质疏松症相关的病理情况下，卵巢切除减少了野生型(WT)小鼠的骨量，这一点已知。有趣的是，正骨虚能抑制卵巢切除引起的骨吸收增加，并保持较高的骨量。此外，Jund虚证还促进了骨髓消融后的新骨形成。对这些观察的分子基础的研究表明，Jund缺乏增加了c-jun、Fra-1和Fra-2在骨骼中的表达水平，同时也增加了Runx2、1型胶原和骨钙素的表达水平。因此，Jund通过抑制骨形成和促进骨吸收的作用参与了雌激素耗竭引起的骨量减少。
JunD is an activator protein-1 (AP-1) component though its function in skeletal system is still not fully understood. To elucidate the role of JunD in the regulation of bone metabolism, we analyzed JunD-deficient mice. JunD deficiency significantly increased bone mass and trabecular number. This bone mass enhancement was due to JunD deficiency-induced increase in bone formation activities in vivo. Such augmentation of bone formation was associated with simultaneous increase in bone resorption while the former was dominant over the latter as accumulation of bone mass occurred in JunD-deficient mice. In a pathological condition relevant to postmenopausal osteoporosis, ovariectomy reduced bone mass in wild type (WT) mice as known before. Interestingly, JunD deficiency suppressed ovariectomy-induced increase in bone resorption and kept high bone mass. In addition, JunD deficiency also enhanced new bone formation after bone marrow ablation. Examination of molecular bases for these observations revealed that JunD deficiency enhanced expression levels of c-jun, fra-1, and fra-2 in bone in conjunction with elevated expression levels of runx2, type 1 collagen, and osteocalcin. Thus, JunD is involved in estrogen depletion-induced osteopenia via its action to suppress bone formation and to enhance bone resorption.