Putative function of TAP63α during endochondral bone formation
- 10 March 2012
- journal article
- Published by Elsevier BV in Gene
- Vol. 495 (2), 95-103
- https://doi.org/10.1016/j.gene.2011.12.057
Abstract
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.Keywords
This publication has 41 references indexed in Scilit:
- Loss of skeletal mineralization by the simultaneous ablation of PHOSPHO1 and alkaline phosphatase function: A unified model of the mechanisms of initiation of skeletal calcificationJournal of Bone and Mineral Research, 2011
- Progressive ankylosis protein (ANK) in osteoblasts and osteoclasts controls bone formation and bone remodelingJournal of Bone and Mineral Research, 2010
- Localization of the Cis-Enhancer Element for Mouse Type X Collagen Expression in Hypertrophic Chondrocytes In VivoJournal of Bone and Mineral Research, 2009
- Pivotal Role of Bcl-2 Family Proteins in the Regulation of Chondrocyte ApoptosisPublished by Elsevier BV ,2008
- Properties of the six isoforms of p63: p53-like regulation in response to genotoxic stress and cross talk with ΔNp73Carcinogenesis: Integrative Cancer Research, 2007
- Dominance of SOX9 function over RUNX2 during skeletogenesisProceedings of the National Academy of Sciences, 2006
- Runx2 inhibits chondrocyte proliferation and hypertrophy through its expression in the perichondriumGenes & Development, 2006
- Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT MethodMethods, 2001
- A new mathematical model for relative quantification in real-time RT-PCRNucleic Acids Research, 2001
- Type X collagen gene expression in mouse chondrocytes immortalized by a temperature-sensitive simian virus 40 large tumor antigen.The Journal of cell biology, 1995