Crowd-based innovaties: verschuivende verantwoordelijkheden in een institutional void

The crowd increasingly plays a key role in facilitating innovations in a variety of sectors, spurred on by IT developments and the concomitant increase in connectivity. Initiatives in this direction, captured under the umbrella term ‘crowd-based innovations’, offer novel opportunities in socio-technical systems by increasing the access, reach and speed of services. At the same time, they signify important challenges because these innovations occur in a context of traditional, well-established institutional and governance structures and practices. This dynamic is captured in the idea of the ‘institutional void’: the tension between traditional structures and (radically) new initiatives. Existing rules, standards and practices are challenged, which raises questions about the safeguarding of public values such as quality, legitimacy, efficiency and governance of crowd-based innovations. This article argues that understanding these tensions requires supplementing empirical research with an explicitly normative dimension to reach thorough and balanced conclusions to facilitate innovation while protecting the valuable elements in existing rules and regulations. Illustrated by a number of short examples, we propose a multidisciplinary research agenda towards formulating appropriate governance structures.The politics and administration of institutional chang

Bovine Colostrum Supplementation and Bone Health: a Pilot Study

Research has shown the positive effects of some bovine colostrum components in bone cells; for instance, lactoferrin is reported to stimulate osteoblast proliferation and inhibit osteoclast activity in cell cultures. However, whether bovine colostrum as a whole can induce bone mass gains in osteoporotic bones is relatively unclear. The aim of this study was to investigate the effects of bovine colostrum supplementation in ovariectomized-induced bone loss (OVX) rats. Methods: Twenty-seven-month-old female Wister rats (n=16) were randomly assigned to the following two groups: 1) a healthy control (non-OVX) with no supplementation, and 2) a OVX with bovine colostrum supplementation (0.5g/day; oral consumption). After 5 months supplementation, bone microstructure was scanned using micro-CT (right tibia). Bone formation markers (serum: pre-and post supplementation) were analysed (alkaline phosphatase and osteocalcin) by ECLIA. The study was approved by the National Ethics Committee for the Use of Animals in Research (ORBEA). Results: No significant differences were found between groups in serum alkaline phosphatase either before or after supplementation (p>0.05). Serum osteocalcin significantly increased post-supple-mentation in the OVX compared to pre-supplementation (pre: 11.32+/-1.61; post: 12.45+/-1.21μg/L, p0.05). Trabecular bone mineral content (BMC), trabecular thickness, cortical bone mineral density (BMD) and cortical BMC were similar between groups after supplementation (p>0.05). However, OVX group revealed significantly higher trabecular porosity (5.6%, p<0.01), trabecular separation (36.3%, p<0.01), and cortical porosity (8.0%, p<0.01) compared to the healthy control post-supplementation. Conclusion: Bovine colostrum seems to preserve bone mass of OVX by stimulating bone formation. However, these positive effects seem not to be sufficient to restore bone micro-architecture in the OVX group, possibly because the administrated dose of bovine colostrum was not sufficient for OVX to catch-up healthy rats in terms of trabecular and cortical porosity. The potential therapeutic use of bovine colostrum for osteoporosis deserves further investigation

Inhibition of the epigenetic suppressor EZH2 primes osteogenic differentiation mediated by BMP2

Bone-stimulatory therapeutics include bone morphogenetic proteins (e.g. BMP2), parathyroid hormone, and antibody-based suppression of WNT antagonists. Inhibition of the epigenetic enzyme enhancer of zeste homolog 2 (EZH2) is both bone anabolic and osteoprotective. EZH2 inhibition stimulates key components of bone-stimulatory signaling pathways, including the BMP2 signaling cascade. Because of high costs and adverse effects associated with BMP2 use, here we investigated whether BMP2 dosing can be reduced by co-treatment with EZH2 inhibitors. Co-administration of BMP2 with the EZH2 inhibitor GSK126 enhanced differentiation of murine (MC3T3) osteoblasts, reflected by increased alkaline phosphatase activity, Alizarin Red staining, and expression of bone-related marker genes (e.g. Bglap and Phospho1). Strikingly, co-treatment with BMP2 (10 ng/ml) and GSK126 (5 μm) was synergistic and was as effective as 50 ng/ml BMP2 at inducing MC3T3 osteoblastogenesis. Similarly, the BMP2-GSK126 co-treatment stimulated osteogenic differentiation of human bone marrow-derived mesenchymal stem/stromal cells, reflected by induction of key osteogenic markers (e.g. Osterix/SP7 and IBSP). A combination of BMP2 (300 ng local) and GSK126 (5 μg local and 5 days of 50 mg/kg systemic) yielded more consistent bone healing than single treatments with either compound in a mouse calvarial critical-sized defect model according to results from μCT, histomorphometry, and surgical grading of qualitative X-rays. We conclude that EZH2 inhibition facilitates BMP2-mediated induction of osteogenic differentiation of progenitor cells and maturation of committed osteoblasts. We propose that epigenetic priming, coupled with bone anabolic agents, enhances osteogenesis and could be leveraged in therapeutic strategies to improve bone mass