Putative function of TAP63α during endochondral bone formation.
Putative function of TAP63α during endochondral bone formation.
复制标题
DOI：
10.1016/j.gene.2011.12.057
复制
发表时间：
2012-03-10
期刊：
影响因子：
3.5
通讯作者：
Zheng Q
中科院分区：
文献类型：
--
作者：
Li F;Lu Y;Ding M;Wu G;Sinha S;Wang S;Zheng Q
P63是P53肿瘤抑制基因家族的成员，在肿瘤的发生、发展过程中发挥着重要作用。有趣的是，以前的研究表明，p63基因缺失的小鼠是不存在的或具有截短的肢体，而人类P63基因突变导致几种骨骼综合征，这些骨骼综合征也显示出肢体和手指异常，这表明它在长骨发育中的重要作用。事实上，我们检测到在肥大MCT细胞（软骨细胞成熟的一种已建立的细胞模型）中p63转录水平比增殖MCT细胞中的p63转录水平增加。为了研究P63在体内对软骨内骨形成的作用，我们建立了转基因小鼠系，其中HA和Flag标记的TAP 63 α（最长的P63亚型）由肥大软骨细胞特异性Col 10a 1调控元件驱动。Col 10a 1-TAP 63 α转基因小鼠在胚胎第17.5天（E17.5）或出生后第1天（P1）的骨骼染色观察到，与其野生型同窝小鼠相比，长骨、趾骨和尾骨的骨化加速，这表明P63在骨骼发育过程中的推定功能。我们还检测到Col 10a 1-TAP 63 α转基因小鼠四肢中Sox 9和Bcl-2转录水平下降，而Alp和Ank略有上调。进一步的免疫组化分析证实了这些小鼠的增殖和肥大区中Sox 9表达的减少。Von Kossa染色表明与同窝对照相比，转基因小鼠肥大区的矿化增加。总之，我们的结果表明TAP 63 α在骨骼发育中的作用。TAP 63 a可能通过与基质矿化和软骨细胞成熟或凋亡相关基因的相互作用促进软骨内骨化
P63, a member of the P53 tumor suppressor family, is known to play important functions in cancer and development. Interestingly, previous studies have shown that p63 null mice are absent or have truncated limbs, while mutations in human P63 cause several skeletal syndromes that also show limb and digit abnormalities, suggesting its essential role in long bone development. Indeed, we detected increased level of p63 transcript in hypertrophic MCT cells (an established cell model of chondrocyte maturation) than in proliferative MCT cells. To investigate the in vivo role of P63 upon endochondral bone formation, we have established transgenic mouse lines in which HA- and Flag-tagged TAP63α (the longest P63 isoform) is driven by the hypertrophic chondrocyte-specific Col10a1 regulatory elements. Skeletal staining of Col10a1-TAP63α transgenic mice at either embryonic day 17.5 (E17.5) or postnatal day 1 (P1) observed accelerated ossification in long bone, digit and tail bones compared to their wild-type littermates, suggesting a putative function of P63 during skeletal development. We also detected decreased level of Sox9 and Bcl-2 transcripts, while Alp and Ank are slightly upregulated in Col10a1-TAP63α transgenic mouse limbs. Further immunohistochemical analysis confirmed the decreased Sox9 expression in the proliferative and hypertrophic zone of these mice. Von Kossa staining suggests increased mineralization in hypertrophic zone of transgenic mice compared to littermate controls. Together, our results suggest a role of TAP63α upon skeletal development. TAP63a may promote endochondral ossification through interaction with genes relevant to matrix mineralization and chondrocyte maturation or apoptosis
登录
查看更多内容
DOI：
10.1046/j.1365-2613.1998.790411.x
发表时间：
1998-10-01
影响因子：
3
作者：
Boot-Handford, RP;Michaelidis, TM;Wallis, GA
通讯作者：
Wallis, GA
影响因子：
64.8
作者：
Mills, AA;Zheng, BH;Bradley, A
通讯作者：
Bradley, A
影响因子：
6.5
作者：
Romano, Rose-Anne;Birkaya, Barbara;Sinha, Satrajit
通讯作者：
Sinha, Satrajit
影响因子：
4.2
作者：
Bonewald, LF;Harris, SE;Boskey, A
通讯作者：
Boskey, A
影响因子：
7.3
作者：
Cheung, JOP;Grant, ME;Hillarby, MC
通讯作者：
Hillarby, MC