Selective deletion of the soluble Colony-Stimulating Factor 1 isoform in vivo prevents estrogen-deficiency bone loss in mice.
Selective deletion of the soluble Colony-Stimulating Factor 1 isoform in vivo prevents estrogen-deficiency bone loss in mice.
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DOI：
10.1038/boneres.2017.22
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发表时间：
2017
期刊：
影响因子：
12.7
通讯作者：
Insogna KL
中科院分区：
文献类型：
--
作者：
Yao GQ;Troiano N;Simpson CA;Insogna KL
体内中和CSF 1可完全防止卵巢切除术（OVX）诱导的小鼠骨丢失。CSF 1有两种亚型，可溶性（sCSF 1）和膜结合型（mCSF 1），但它们各自的生物学功能尚不清楚。先前已报道mCSF 1敲除（K/O）和野生型（Wt）雌性小鼠在OVX后经历相同程度的骨丢失。在野生型小鼠中，sCSF 1的表达在OVX后骨骼组织中升高了4倍，而mCSF 1的表达没有变化。为了检查sCSF 1在OVX诱导的骨丢失中的作用，对小鼠进行工程改造，其中sCSF 1不表达，但mCSF 1的表达不受影响（sCSF 1 K/O）。异构体特异性逆转录PCR证实了从这些动物中分离的骨组织中不存在sCSF 1的转录物，并且通过ELISA未检测到循环CSF 1。令人惊讶的是，通过双能X射线吸收测定法和micro-CT评估，sCSF 1 K/O小鼠和Wt对照组之间的骨矿物质密度（BMD）无显著差异。然而，OVX后1个月，与假手术组相比，OVX-Wt动物的股骨、脊柱和总BMD分别下降了11.2%、8.9%和8.7%。相比之下，与假手术OVX sCSF 1 K/O小鼠相比，OVX sCSF 1 K/O小鼠在相同的3个位点显示出+0.1%、-2.4%和+2.3%的变化。这些数据表明CSF 1的两种亚型具有重要的非冗余功能，并表明sCSF 1而不是mCSF 1在雌激素缺乏性骨丢失中起关键作用。
Neutralizing CSF1 in vivo completely prevents ovariectomy (OVX)-induced bone loss in mice. There are two isoforms of CSF1, soluble (sCSF1), and membrane-bound (mCSF1), but their individual biological functions are unclear. It had been previously reported that mCSF1 knockout (K/O) and wild type (Wt) female mice experience the same degree of bone loss following OVX. In Wt mice the expression of sCSF1 was elevated fourfold in skeletal tissue following OVX while expression of mCSF1 was unchanged. To examine the role of sCSF1 in OVX-induced bone loss, mice were engineered in which sCSF1 was not expressed but expression of mCSF1 was unaffected (sCSF1 K/O). Isoform-specific reverse transcription PCR confirmed the absence of transcripts for sCSF1 in bone tissue isolated from these animals and no circulating CSF1 was detected by ELISA. Surprisingly, there were no significant differences in bone mineral density (BMD) between sCSF1 K/O mice and Wt controls as assessed by dual-energy X-ray absorptiometry and micro-CT. However, one month after OVX, femoral, spinal and total BMD had declined by 11.2%, 8.9%, and 8.7% respectively in OVX-Wt animals as compared to Sham-OVX. In contrast OVX sCSF1 K/O mice showed changes of +0.1%, −2.4%, and +2.3% at the same 3 sites compared to Sham-OVX sCSF1 K/O mice. These data indicate important non-redundant functions for the two isoforms of CSF1 and suggest that sCSF1, but not mCSF1, plays a key role in estrogen-deficiency bone loss.
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影响因子：
4.9
作者：
Garcia S;Hartkamp LM;Malvar-Fernandez B;van Es IE;Lin H;Wong J;Long L;Zanghi JA;Rankin AL;Masteller EL;Wong BR;Radstake TR;Tak PP;Reedquist KA
通讯作者：
Reedquist KA
影响因子：
64.5
作者：
Cooper TA;Wan L;Dreyfuss G
通讯作者：
Dreyfuss G
影响因子：
4.8
作者：
INSOGNA, KL;STEWART, AF;BROADUS, AE
通讯作者：
BROADUS, AE
影响因子：
15.9
作者：
Cenci, S;Weitzmann, MN;Pacifici, R
通讯作者：
Pacifici, R
影响因子：
56.9
作者：
KAWASAKI, ES;LADNER, MB;MARK, DF
通讯作者：
MARK, DF