Mesenchymal cell TRPM7 expression is required for bone formation via the regulation of chondrogenesis.
Mesenchymal cell TRPM7 expression is required for bone formation via the regulation of chondrogenesis.
复制标题
间充质细胞 TRPM7 表达是通过调节软骨形成来形成骨所必需的。
作者：
Shin M;Mori S;Mizoguchi T;Arai A;Kajiya H;Okamoto F;Bartlett JD;Matsushita M;Udagawa N;Okabe K
瞬时受体电位褪化抑素亚家族成员7 （TRPM7）是一种双功能蛋白，含有融合到阳离子渗透的离子通道的激酶，包括Ca2+和Mg2+。trpm7缺失小鼠显示胚胎致死。配对相关同源盒1 （Prx1）在未分化的间充质细胞中表达，如参与肢体骨骼形成的软骨细胞和成骨细胞的祖细胞。生成prx1 - cre依赖性TRPM7间充质缺失小鼠，以检测TRPM7在骨发育中的作用。我们发现prx1 - cre；Trpm7fl/ fl小鼠骨骼缩短，骨小梁形成受损。骨小梁参数，如骨体积（BV/TV）、骨小梁数(Tb。N)， prx1 - cre、Trpm7fl/flmice均降低。皮质骨参数皮质骨面积（Ct.Ar）和皮质骨厚度（Ct.Th）均下调。prx1 - cre骨形成率；Trpm7fl/flmice没有变化，但该区的肥厚面积和细胞大小变小，col2a1、col10a1和mmp13的表达较对照小鼠下调。这些发现提示prx1 - cre的软骨形成受损；Trpm7fl/flmice与对照小鼠比较。核因子- κ B配体受体激活因子（RANKL）表达升高，RANKL阳性细胞和破骨细胞在生长板与骨小梁交界区明显聚集。相比之下，TRPM7 KR小鼠是激酶死亡突变体，其TRPM7离子通道功能没有改变，与野生型小鼠相比，其小梁或皮质骨参数没有显着差异。这些发现表明，TRPM7在骨发育中作为阳离子通道而不是作为激酶调节软骨形成至关重要。
Transient receptor potential melastatin-subfamily member 7 (TRPM7) is a bifunctional protein containing a kinase fused to an ion channel permeated with cations, including Ca2+and Mg2+.Trpm7-null mice show embryonic lethality. Paired related homeobox 1 (Prx1) is expressed in undifferentiated mesenchymal cells such as the progenitor cells of both chondrocytes and osteoblasts involved in limb skeleton formation.Prx1-Cre-dependentTrpm7mesenchymal-deleted mice were generated to examine the role of TRPM7 in bone development. We found thatPrx1-Cre;Trpm7fl/flmice had shortened bones and impaired trabecular bone formation. Trabecular bone parameters, such as the bone volume (BV/TV), and trabecular number (Tb.N), were decreased inPrx1-Cre;Trpm7fl/flmice. The cortical bone parameters of cortical bone area (Ct.Ar) and cortical bone thickness (Ct.Th) were also down-regulated in these mice. The bone formation rate inPrx1-Cre;Trpm7fl/flmice was unchanged, but the hypertrophic area and cell size of the zone were smaller, and the expression ofCol2a1,Col10a1andMmp13was downregulated compared with control mice. These findings suggest impaired chondrogenesis inPrx1-Cre;Trpm7fl/flmice compared to control mice. The receptor activator of nuclear factor-kappa B ligand (RANKL) expression was increased, and RANKL-positive cells and osteoclasts were markedly accumulated in the boundary region between the growth plate and trabecular bone. In contrast, TRPM7 KR mice, which are kinase-dead mutants in which the TRPM7 ion channel function has not been altered, showed no marked differences in trabecular or cortical bone parameters compared to wild-type mice. These findings suggest that TRPM7 is critical as a cation channel rather than as a kinase in bone developmentviathe regulation of chondrogenesis.
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TRPM7通道函数中的缺陷通过改变的细胞MG（2+）稳态和细胞骨架结构来消除血小板。
影响因子：
16.6
作者：
Stritt S;Nurden P;Favier R;Favier M;Ferioli S;Gotru SK;van Eeuwijk JM;Schulze H;Nurden AT;Lambert MP;Turro E;Burger-Stritt S;Matsushita M;Mittermeier L;Ballerini P;Zierler S;Laffan MA;Chubanov V;Gudermann T;Nieswandt B;Braun A
通讯作者：
Braun A
影响因子：
11.8
作者：
Mizoguchi, Toshihide;Pinho, Sandra;Ahmed, Jalal;Kunisaki, Yuya;Hanoun, Maher;Mendelson, Avital;Ono, Noriaki;Kronenberg, Henry M.;Frenette, Paul S.
通讯作者：
Frenette, Paul S.
DOI：
10.1242/dev.137489
发表时间：
2016-10-15
期刊：
Development (Cambridge, England)
影响因子：
--
作者：
Houben A;Kostanova-Poliakova D;Weissenböck M;Graf J;Teufel S;von der Mark K;Hartmann C
通讯作者：
Hartmann C
影响因子：
4
作者：
Kajiya, Hiroshi;Okamoto, Fujio;Okabe, Koji
通讯作者：
Okabe, Koji
影响因子：
12.8
作者：
Kang SS;Shin SH;Auh CK;Chun J
通讯作者：
Chun J