Although many regulators of skeletogenesis have been functionally characterized, one current challenge is to integrate this information into regulatory networks. Here, we discuss how the canonical Wnt and Smad‐dependent BMP pathways interact together and play antagonistic or cooperative roles at different steps of osteogenesis, in the context of the developing vertebrate embryo. Early on, BMP signaling specifies multipotent mesenchymal cells into osteochondroprogenitors. In turn, the function of Wnt signaling is to drive these osteochondroprogenitors towards an osteoblastic fate. Subsequently, both (...) pathways promote osteoblast differentiation, albeit with notable mechanistic differences. In osteocytes, the ultimate stage of osteogenic differentiation, the Wnt and BMP pathways exert opposite effects on the control of bone resorption by osteoclasts. We describe how the dynamic molecular wiring of the canonical Wnt and Smad‐dependent BMP signaling into the skeletal cell genetic programme is critical for the generation of bone‐specific cell types during development. (shrink)

BackgroundSerious ethical problems have been anecdotally identified in the care of children with osteogenesis imperfecta (OI), which may negatively impact their moral experiences, defined as their sense of fulfillment towards personal values and beliefs.Research aimsTo explore children’s actual and desired participation in discussions, decisions, and actions in an OI hospital setting and their community using art-making to facilitate their self-expression.Research designA focused ethnography was conducted using the moral experiences framework with data from key informant interviews; participant observations, semi-structured interviews, (...) and practice-based research (art-making) with 10 children with OI; and local documents.Participants and research contextThe study was conducted at a pediatric, orthopedic hospital.Ethical considerationsThis study was approved by McGill University Institutional Review Board.Findings/resultsChildren expressed desires to participate in their care, but sometimes lacked the necessary resources and encouragement from healthcare providers. Art-making facilitated children’s voice and participation in health-related discussions.ConclusionsHealthcare providers are recommended to consider the benefits of art-making and educational resources to reduce discrepancies between children’s actual and desired participation in care and promote positive moral experiences. (shrink)

Genetic testing can be used to determine if unexplained fractures in children could have resulted from a predisposition to bone fractures, e.g., osteogenesis imperfecta. However, uncertainty is introduced if a variant of unknown significance is identified. Proper interpretation of VUS in these situations is critical because of its influence on clinical care and in court rulings. This study sought to understand how VUS are interpreted and used by practitioners when there is a differential diagnosis including both osteogenesis imperfecta (...) and non-accidental injury.A 15-question survey was emailed to physicians who requested analysis of two genes, COL1A1 and COL1A2, from the University of Washington from 2005-2013 for patient cases involving suspicion of child abuse.Among the 89 participants, responses differed about when genetic testing should be ordered for osteogenesis imperfecta, who should be consulted about utilization of VUS test results, follow-up procedures, and who should receive the VUS results.There are no clear guidelines for how to interpret and follow up on VUS. In the legal setting, misinterpreted VUS could lead to unintended consequences and deleterious ramifications for family members. The need for better practice guidelines to help promote more equitable handling of these sensitive legal cases is clear. (shrink)

An increasing number of people worldwide are living with chronic conditions that have an aspect of bodily fragility as part of the condition or as an effect of treatment. In this article, I explore the temporal experience of bodily fragility and the particularities of consciousness states among people with the chronic condition osteogenesis imperfecta (OI) in Denmark. My aim is threefold. First, my goal is to give an insight into life with OI, a rare and rarely studied condition. Second, (...) I shed light on bodily fragility, a theme that lives in the shadows of other analytical foci in anthropology. Third, I will contribute to the anthropological understanding of the connection among body, physical environment, and consciousness. I argue that the lifeworlds of people with OI are haunted by mental and bodily memories and fearful future scenarios, which makes the past and the future collapse into the present. (shrink)

Staggering advances in biotechnology within the past decade have given rise to pharmacological, surgical and prosthetic techniques capable of enhancing human functioning rather than merely treating or preventing disease. Bioenhancement technologies range from nootropics capable of enhancing cognitive abilities to distraction osteogenesis, a surgical technique capable of increasing height through limb lengthening. This paper examines whether the use of bioenhancements falls inside or outside the proper boundaries of healthcare, and if so, whether clinicians have professional responsibilities to administer bioenhancements (...) to patients. After explicating two theoretical approaches to the concept of health, one objectivist and the other constructivist, I contend that clinicians' corresponding professional responsibilities hinge on which philosophical account of health is endorsed, and illustrate how the lack of analytic clarity with respect to this concept can lead to defective positions on the place of bioenhancements in healthcare. With this conceptual framework in place, an account of health as a cluster concept that incorporates both constructivist and objectivist components is developed and defended. (shrink)

This article considers aspects of a development aid that provides medical support to strengthen pediatric orthopedics in Rwanda. We present part of the Afriquia foundation work, a nonprofit foundation from Poland involved in supporting the medical sector in Rwanda as a sign of global solidarity and the human right to health. The main foundation's activity is the treatment of orthopedic problems among Rwandan citizens. We present a case study of two children under the care of the Afiquia foundation. 11‐year‐old Seraphine (...) treated due to the consequences of right tibia osteomyelitis and 11‐year‐old Lavi suffering from osteogenesis imperfecta. Both children were treated surgically in Poland due to Rwanda's lack of treatment possibilities. After the applied treatment, Seraphine walks correctly without crutches and can attend school and thrive among her peers. Lavi has not sustained any fragility fracture since the surgery in Poland. He is healthy and constantly ongoing his rehabilitation including gait training. The described cases initiated development aid in Rwanda, supplying hospitals with orthopedic implants and training medical staff. The growing number of humanitarian crises across the globe and the people affected requires increasing organizations involved in providing relief. The emphasis should be on global education, aiming to make the recipients reflect and prepare them to face humanitarian crises. (shrink)

Hedgehog is an important morphogenic signal that directs pattern formation during embryogenesis, but its activity also remains present through adult life. It is now becoming increasingly clear that during the reproductive phase of life and beyond it continues to direct cell renewal (which is essential to combat the chronic environmental stress to which the body is constantly exposed) and counteracts vascular, osteolytic and sometimes oncological insults to the body. Conversely, down‐regulation of hedgehog signalling is associated with ageing‐related diseases such as (...) type 2 diabetes, neurodegeneration, atherosclerosis and osteoporosis. Hence, in this essay we argue that hedgehog signalling is not only important at the start of life, but also constitutes an important anti‐geriatric influence, and that enhanced understanding of its properties may contribute to developing rational strategies for healthy ageing and prevention of ageing‐related diseases.Also watch the Video Abstract. (shrink)