Department of Genetics and Development, Columbia University Medical Center, New York, NY 10032, USA.
Department of Genetics and Development, Columbia University Medical Center, New York, NY 10032, USA.
Mol Metab. 2017 Dec;6(12):1610-1615. doi: 10.1016/j.molmet.2017.10.001. Epub 2017 Oct 6.
That the bone-derived hormone osteocalcin is necessary to promote normal brain development and function, along with its recently described sufficiency in reversing cognitive manifestations of aging, raises novel questions. One of these is to assess whether bone health, which deteriorates rapidly with aging, is a significant determinant of cognition and anxiety-like behavior.
To begin addressing this question, we used mice haploinsufficient for Runx2, the master gene of osteoblast differentiation and the main regulator of Osteocalcin expression. Control and Runx2+/- mice were evaluated for the expression of osteocalcin's target genes in the brain and for behavioral parameters, using two assays each for cognition and anxiety-like behavior.
We found that adult Runx2+/- mice had defects in bone resorption, reduced circulating levels of bioactive osteocalcin, and reduced expression of osteocalcin's target genes in the brain. Consequently, they had significant impairment in cognitive function and increased anxiety-like behavior.
These results indicate that bone remodeling is a determinant of brain function.
骨源性激素骨钙素对于促进正常大脑发育和功能是必要的，其最近被描述为能够逆转衰老的认知表现，这引发了新的问题。其中之一是评估随着年龄增长而迅速恶化的骨骼健康是否是认知和类似焦虑行为的重要决定因素。
为了开始解决这个问题，我们使用了 Runx2 单倍体不足的小鼠，Runx2 是成骨细胞分化的主基因，也是骨钙素表达的主要调节剂。使用两种认知和两种类似焦虑行为的测试方法，评估了控制和 Runx2+/- 小鼠大脑中骨钙素靶基因的表达以及行为参数。
我们发现成年 Runx2+/- 小鼠存在破骨细胞吸收缺陷、循环中生物活性骨钙素水平降低以及大脑中骨钙素靶基因表达减少的情况。因此，它们的认知功能显著受损，并且表现出类似焦虑的行为增加。
这些结果表明，骨骼重塑是大脑功能的决定因素。
