Vascular endothelial growth factor (VEGF) is a critical regulator of angiogenesis during development, but little is known about the factors that control its expression. We provide the first example of tissue specific loss of VEGF expression as a result of targeting a single gene, Cbfa1/Runx2. During endochondral bone formation, invasion of blood vessels into cartilage is associated with upregulation of VEGF in hypertrophic chondrocytes and increased expression of VEGF receptors in the perichondrium. This upregulation is lacking in Cbfa1 deficient mice, and cartilage angiogenesis does not occur. Finally, over-expression of Cbfa1 in fibroblasts induces an increase in their VEGF mRNA level and protein production by stimulating VEGF transcription. The results demonstrate that Cbfa1 is a necessary component of a tissue specific genetic program that regulates VEGF during endochondral bone formation.

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BackgroundAdult smoking has its roots in adolescence. If individuals do not initiate smoking during this period it is unlikely they ever will. In high income countries, smoking rates among Indigenous youth are disproportionately high. However, despite a wealth of literature in other populations, there is less evidence on the determinants of smoking initiation among Indigenous youth. The aim of this study was to explore the determinants of smoking among Australian Indigenous young people with a particular emphasis on the social and cultural processes that underlie tobacco use patterns among this group.MethodsThis project was undertaken in northern Australia. We undertook group interviews with 65 participants and individual in-depth interviews with 11 youth aged 13–20 years led by trained youth ‘peer researchers.’ We also used visual methods (photo-elicitation) with individual interviewees to investigate the social context in which young people do or do not smoke. Included in the sample were a smaller number of non-Indigenous youth to explore any significant differences between ethnic groups in determinants of early smoking experiences. The theory of triadic influence, an ecological model of health behaviour, was used as an organising theory for analysis.ResultsFamily and peer influences play a central role in smoking uptake among Indigenous youth. Social influences to smoke are similar between Indigenous and non-Indigenous youth but are more pervasive (especially in the family domain) among Indigenous youth. While Indigenous youth report high levels of exposure to smoking role models and smoking socialisation practices among their family and social networks, this study provides some indication of a progressive denormalisation of smoking among some Indigenous youth.ConclusionsFuture initiatives aimed at preventing smoking uptake in this population need to focus on changing social normative beliefs around smoking, both at a population level and within young peoples’ immediate social environment. Such interventions could be effectively delivered in both the school and family environments. Specifically, health practitioners in contact with Indigenous families should be promoting smoke free homes and other anti-smoking socialisation behaviours.