Kawamata Aya, Izu Yayoi, Yokoyama Haruna, Amagasa Teruo, Wagner Erwin F, Nakashima Kazuhisa, Ezura Yoichi, Hayata Tadayoshi, Noda Masaki
Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, 2-3-10 Kanda-Surugadai, Chiyoda-ku, 101-0062, Tokyo, Japan.
J Cell Biochem. 2008 Mar 1;103(4):1037-45. doi: 10.1002/jcb.21660.
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 I collagen, and osteocalcin. Thus, JunD is involved in estrogen depletion-induced osteopenia via its action to suppress bone formation and to enhance bone resorption.
JunD是活化蛋白-1（AP-1）的一个组成部分，尽管其在骨骼系统中的功能仍未完全明确。为了阐明JunD在骨代谢调节中的作用，我们分析了JunD基因敲除小鼠。JunD基因敲除显著增加了骨量和骨小梁数量。这种骨量增加是由于JunD基因敲除在体内诱导骨形成活性增加所致。这种骨形成的增强与骨吸收同时增加相关，而在JunD基因敲除小鼠中，由于骨量积累，前者比后者更占主导。在与绝经后骨质疏松症相关的病理状态下，卵巢切除如之前所知会降低野生型（WT）小鼠的骨量。有趣的是，JunD基因敲除抑制了卵巢切除诱导的骨吸收增加，并保持了高骨量。此外，JunD基因敲除还增强了骨髓消融后的新骨形成。对这些观察结果的分子基础研究表明，JunD基因敲除会增强骨中c-jun、fra-1和fra-2的表达水平，同时也会提高runx2、I型胶原蛋白和骨钙素的表达水平。因此，JunD通过其抑制骨形成和增强骨吸收的作用参与雌激素缺乏诱导的骨质减少。
