Runx2 haploinsufficiency ameliorates the development of ossification of the posterior longitudinal ligament.
Runx2 haploinsufficiency ameliorates the development of ossification of the posterior longitudinal ligament.
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DOI：
10.1371/journal.pone.0043372
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Takeda S
中科院分区：
文献类型：
--
作者：
Iwasaki M;Piao J;Kimura A;Sato S;Inose H;Ochi H;Asou Y;Shinomiya K;Okawa A;Takeda S
后纵韧带骨化是一种以韧带异位钙化为特征的疾病，其发病机制尚不清楚。我们试图确定Runx 2在OPLL发病机制中的体内作用，Runx 2是成骨细胞分化和骨骼矿化的主要调节因子。使用原位杂交和免疫组织化学，并通过监测插入Runx 2基因位点的LacZ基因的活性，检查Runx 2在韧带中的表达。为了研究Runx 2的功能作用，我们研究了ENPP 1 ttw/ttw小鼠，一种OPLL的小鼠模型，与杂合子Runx 2小鼠杂交以降低Runx 2的表达，我们使用3D-microCT进行了组织学和定量放射学分析。Runx 2在野生型小鼠的韧带中表达。Runx 2表达的诱导先于ENPP 1 ttw/ttw小鼠OPLL样区域异位钙化的发展。Runx 2单倍不足改善了ENPP 1 ttw/ttw小鼠异位钙化的发展。总的来说，这项研究表明，Runx 2在OPLL样区域表达，其升高是在OPLL小鼠模型中形成完整OPLL样表型的先决条件。
Ossification of the Posterior Longitudinal Ligament (OPLL) is a disease that is characterized by the ectopic calcification of the ligament; however, the pathogenesis of OPLL remains to be investigated. We attempted to identify the in vivo role of Runx2, a master regulator of osteoblast differentiation and skeletal mineralization, in the pathogenesis of OPLL. The expression of Runx2 in the ligament was examined using in situ hybridization and immunohistochemistry and by monitoring the activity of a LacZ gene that was inserted into the Runx2 gene locus. To investigate the functional role of Runx2, we studied ENPP1ttw/ttw mice, a mouse model of OPLL, that were crossed with heterozygous Runx2 mice to decrease the expression of Runx2, and we performed histological and quantitative radiological analyses using 3D-micro CT. Runx2 was expressed in the ligament of wild-type mice. The induction of Runx2 expression preceded the development of ectopic calcification in the OPLL-like region of the ENPP1ttw/ttw mice. Runx2 haploinsufficiency ameliorated the development of ectopic calcification in the ENPP1ttw/ttw mice. Collectively, this study demonstrated that Runx2 is expressed in an OPLL-like region, and its elevation is a prerequisite for developing the complete OPLL-like phenotype in a mouse model of OPLL.
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影响因子：
3.8
作者：
Kim, Dong Hwan;Jeong, Yong Seol;Yun, Dong Hwan
通讯作者：
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影响因子：
4.2
作者：
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影响因子：
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作者：
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McKee, Marc D.
影响因子：
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通讯作者：
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影响因子：
3
作者：
Kamiya, M;Harada, A;Yamada, Y
通讯作者：
Yamada, Y