Angiotensin receptor I stimulates osteoprogenitor proliferation through TGFβ-mediated signaling

Clinical studies of large human populations and pharmacological interventions in rodent models have recently suggested that anti-hypertensive drugs that target angiotensin II (Ang II) activity may also improve loss of bone mineral density. Here we identified in a genetic screen the Ang II type I receptor (AT1R) as a potential determinant of osteogenic differentiation and, implicitly, bone formation. Silencing of AT1R expression by RNA interference severely impaired the maturation of a multipotent mesenchymal cell line (W20-17) along the osteoblastic lineage. The same effect was also observed after the addition of the AT1R antagonist losartan but not the AT2R inhibitor PD123,319. Additional cell culture assays traced the time of greatest losartan action to the early stages of W20-17 differentiation, namely during cell proliferation. Indeed, addition of Ang II increased proliferation of differentiating W20-17 and primary mesenchymal stem cells and this stimulation was reversed by losartan treatment. Cells treated with losartan also displayed an appreciable decrease of activated (phosphorylated)-Smad2/3 proteins. Moreover, Ang II treatment elevated endogenous transforming growth factor β (TGFβ) expression considerably and in an AT1R-dependent manner. Finally, exogenous TGFβ was able to restore high proliferative activity to W20-17 cells that were treated with both Ang II and losartan. Collectively, these results suggest a novel mechanism of Ang II action in bone metabolism that is mediated by TGFβ and targets proliferation of osteoblast progenitors.

Towards Empowerment: Narrative Study of Counselling Psychology Trainees and How They Make Sense of Their Personal and Professional Development in the Context of Their Past Experiences

The discipline of counselling psychology continues to grow and change in response to social, economic and political pressures. It has been argued that its quest for a coherent and distinct identity, which emphasises the possibility of the coexistence of multiple approaches, creates an inherently uncertain and dilemmatic training environment that may hinder the development of trainees’ professional identities. In order to gain a deeper understanding of the issue at hand, the aim was to explore how final year trainees and newly qualified counselling psychologists constructed and made sense of their emerging professional identities and what experiences, past and present, they drew upon in the context of their training to shape those identities. Applying narrative inquiry to analyse eight open-ended interviews, eight preliminary themes were originally identified in participants’ narratives, which with further refinements lead to stories of struggle and marginalisation, growth and discovery, and power and resilience. Participants’ stories of struggle and marginalisation emerged in reference to early family dynamics and stressful life experiences, which seemed to also foster a strong identification with the counselling psychology profession, while stories of growth and discovery focused on the importance of having supportive figures, who helped to instill a sense of security and create an atmosphere of openness. It was in this learning environment that participants felt it was possible to develop a more resilient, empowered professional self, which allowed them to shed an earlier sense of struggle and vulnerability. However, where more of an emphasis was placed on power and resilience, there seemed to be less room for participants to express other feelings that came into conflict with their preferred sense of professional self. While there seems to be a need for a ‘safer’ climate, in which trainees could voice and acknowledge anxieties, vulnerabilities and limitations, addressing concerns around power and vulnerability that may be contributing to the silencing of particular voices and identities may be equally important if trainees are to develop coherent and distinct counselling psychologist identities.