title: Putative function of TAP63α during endochondral bone formation.
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.
authors.affiliation: Department of Anatomy and Cell Biology, Rush University Medical Center, Chicago, IL 60612, USA.
authors.forename: Feifei
authors.initials: F
authors.lastname: Li
authors.forename: Yaojuan
authors.initials: Y
authors.lastname: Lu
authors.forename: Ming
authors.initials: M
authors.lastname: Ding
authors.forename: Guojun
authors.initials: G
authors.lastname: Wu
authors.forename: Satrajit
authors.initials: S
authors.lastname: Sinha
authors.forename: Siying
authors.initials: S
authors.lastname: Wang
authors.forename: Qiping
authors.initials: Q
authors.lastname: Zheng
mesh_terms: D000818:Animals; D001857:Bone Matrix / Q000502:physiology; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism*; D024121:Collagen Type X / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D015576:Hyperostosis / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D009687:Nuclear Proteins / Q000235:genetics; D010012:Osteogenesis / Q000502:physiology*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D055758:SOX9 Transcription Factor / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: C570620:Col10a1 protein, mouse; D024121:Collagen Type X; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D019253:Proto-Oncogene Proteins c-bcl-2; D055758:SOX9 Transcription Factor; C527933:Sox9 protein, mouse; D015534:Trans-Activators; C486419:Trp63 protein, mouse; C000606368:Trp73 protein, mouse; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins