Bone growth and turnover in progesterone receptor knockout mice
Bone growth and turnover in progesterone receptor knockout mice
复制标题
DOI：
10.1210/en.2007-1247
复制
发表时间：
2008-05-01
期刊：
影响因子：
4.8
通讯作者：
Turner, Russell T.
中科院分区：
文献类型：
--
作者：
Rickard, David J.;Iwaniec, Urszula T.;Turner, Russell T.
黄体酮受体（PR）信号在骨骼代谢中的作用一直存在争议。为了确定通过PR传递的信号是否对正常的骨生长和转换是必要的，我们对纯合子雌性PR敲除（PRKO）小鼠在6、12和26周龄时的骨骼进行了组织形态学和显微计算机断层扫描分析。这些小鼠具有PR位点的零突变，阻断PR的a和B亚型的基因表达。PRKO小鼠的体重增加、子宫体重增加和胫骨纵向骨生长正常。相比之下，12周龄PRKO小鼠肱骨的总骨量、松质骨量和皮质骨量增加，而胫骨的皮质骨量和松质骨量正常。26周龄时，PRKO小鼠胫骨近端干骺端松质骨面积比同龄野生型小鼠大153%。6个月大的PRKO小鼠松质骨平衡的改善与骨形成升高和破骨细胞周长减少的趋势有关。综上所述，这些发现表明，小鼠体内的PR信号对于骨骼生长和更新并不是必需的。然而，在一些骨骼部位，PR信号减弱了青春期皮质和松质骨量的积累。
The role of progesterone receptor (PR) signaling in skeletal metabolism is controversial. To address whether signaling through the PR is necessary for normal bone growth and turnover, we performed histomorphometric and microcomputed tomography analyses of bone from homozygous female PR knockout (PRKO) mice at 6, 12, and 26 wk of age. These mice possess a null mutation of the PR locus, which blocks the gene expression of A and B isoforms of PR. Body weight gain, uterine weight gain, and tibia longitudinal bone growth were normal in PRKO mice. In contrast, total, cancellous, and cortical bone mass were increased in the humerus of 12-wk-old PRKO mice, whereas cortical and cancellous bone mass in the tibia was normal. At 26 wk of age, cancellous bone area in the proximal tibia metaphysis of PRKO mice was 153% greater than age matched wild-type mice. The improved cancellous bone balance in 6-month-old PRKO mice was associated with elevated bone formation and a tendency toward reduced osteoclast perimeter. Taken together, these findings suggest that PR signaling in mice is not essential for bone growth and turnover. However, at some skeletal sites, PR signaling attenuates the accumulation of cortical and cancellous bone mass during adolescence.