The role of the P2X7 receptor on bone loss in a mouse model of inflammation-mediated osteoporosis

In inflammatory autoimmune diseases, bone loss is frequent. In most cases, secondary osteoporosis is caused by treatment with systemic glucocorticoid. However, the pathogenesis behind the bone loss is presumed multifactorial. We aimed to elucidate the role of the P2X7 receptor on bone mineral density (BMD), microarchitecture, and bone strength in a standardized mouse model of inflammation-mediated osteoporosis (IMO). In total 146 mice completed our protocol, 70 wild type (WT) mice and 76 P2X7−/− (knockout, KO). BMD at the femur and spine decreased significantly from baseline to day 20 in the WT IMO mice (p < 0.01). In the WT vehicle, KO vehicle and KO IMO, no significant BMD changes were found. Bone strength showed a lower mid-shaft max strength (p = 0.038) and also a non-significant trend towards lower strength at the femoral neck of the WT IMO group. Trabecular bone volume fraction (BV/TV) and connectivity density (CD) after 20 days were significantly decreased in the WT IMO group (p = 0.001). In contrast, the WT vehicle and KO vehicle, BV/TV and CD did no change at 20 days. Cortical bone revealed no significant microarchitectural changes after 20 days in the WT IMO group, whereas the total cortical area increased significantly in WT vehicle and KO IMO after 20 days (5.2% and 8.8%, respectively). In conclusion, the P2X7 receptor KO mice did not respond to inflammation with loss of BMD whereas the WT mice had a significant loss of BMD, bone strength and trabecular microarchitecture, demonstrating a role for the P2X7 receptor in inflammatory bone loss

Genetic background strongly influences the bone phenotype of P2X7 receptor knockout mice

The purinergic P2X7 receptor is expressed by bone cells and has been shown to be important in both bone formation and bone resorption. In this study we investigated the importance of the genetic background of the mouse strains on which the P2X7 knock-out models were based by comparing bone status of a new BALB/cJ P2X7-/- strain with a previous one based on the C57BL/6 strain. Female four-month-old mice from both strains were DXA scanned on a PIXImus densitometer; femurs were collected for bone strength measurements and serum for bone marker analysis. Bone-related parameters that were altered only slightly in the B6 P2X7-/- became significantly altered in the BALB/cJ P2X7-/- when compared to their wild type littermates. The BALB/cJ P2X7-/- showed reduced levels of serum C-telopeptide fragment (s-CTX), higher bone mineral density, and increased bone strength compared to the wild type littermates. In conclusion, we have shown that the genetic background of P2X7-/- mice strongly influences the bone phenotype of the P2X7-/- mice and that P2X7 has a more significant regulatory role in bone remodeling than found in previous studies

Extracellular ATP released by osteoblasts is a key local inhibitor of bone mineralisation

Previous studies have shown that exogenous ATP (>1µM) prevents bone formation in vitro by blocking mineralisation of the collagenous matrix. This effect is thought to be mediated via both P2 receptor-dependent pathways and a receptor-independent mechanism (hydrolysis of ATP to produce the mineralisation inhibitor pyrophosphate, PPi). Osteoblasts are also known to release ATP constitutively. To determine whether this endogenous ATP might exert significant biological effects, bone-forming primary rat osteoblasts were cultured with 0.5-2.5U/ml apyrase (which sequentially hydrolyses ATP to ADP to AMP + 2Pi). Addition of 0.5U/ml apyrase to osteoblast culture medium degraded extracellular ATP to <1% of control levels within 2 minutes; continuous exposure to apyrase maintained this inhibition for up to 14 days. Apyrase treatment for the first 72 hours of culture caused small decreases (≤25%) in osteoblast number, suggesting a role for endogenous ATP in stimulating cell proliferation. Continuous apyrase treatment for 14 days (≥0.5U/ml) increased mineralisation of bone nodules by up to 3-fold. Increases in bone mineralisation were also seen when osteoblasts were cultured with the ATP release inhibitors, NEM and brefeldin A, as well as with P2X1 and P2X7 receptor antagonists. Apyrase decreased alkaline phosphatase (TNAP) activity by up to 60%, whilst increasing the activity of the PPi-generating ecto-nucleotide pyrophosphatase/phosphodiesterases (NPPs) up to 2.7-fold. Both collagen production and adipocyte formation were unaffected. These data suggest that nucleotides released by osteoblasts in bone could act locally, via multiple mechanisms, to limit mineralisation

UN plastic treaty must mind the people: Citizen science can assist citizen involvement in plastic policymaking

By 2024, the United Nations treaty to end all plastic pollution is set to join multilateral forces to act on plastic pollution. While involving citizens has the potential to improve policy implementation, legitimacy, and relevance, effective measures are currently lacking in plastic pollution policy. Here, we aim to build on existing praxis in the European Union and analyze current initiatives engaging citizens. We discuss these in a citizen science context and provide recommendations for an effective treaty. We find that current measures are inadequate, that policy impact is contingent on the policy phases and the input type, and we highlight opportunities for citizen science to support public access to policy influence. We recommend that the upcoming treaty ensures access throughout the policy process, that inputs are systematized and harmonized to increase application and policy uptake, and finally, consistent equity in participation for citizens affected by plastic pollution

Ambient air pollution in relation to diabetes and glucose-homoeostasis markers in China: a cross-sectional study with findings from the 33 Communities Chinese Health Study

Background: Health effects of air pollution on diabetes have been scarcely studied in developing countries. We aimed to explore the associations of long-term exposure to ambient particulate matter (PM) and gaseous pollutants with diabetes prevalence and glucose-homoeostasis markers in China. Methods: Between April 1 and Dec 31, 2009, we recruited a total of 15 477 participants aged 18–74 years using a random number generator and a four-staged, stratified and cluster sampling strategy from a large cross-sectional study (the 33 Communities Chinese Health Study) from three cities in Liaoning province, northeastern China. Fasting and 2 h insulin and glucose concentrations and the homoeostasis model assessment of insulin resistance index and β-cell function were used as glucose-homoeostasis markers. Diabetes was defined according to the American Diabetes Association's recommendations. We calculated exposure to air pollutants using data from monitoring stations (PM with an aerodynamic diameter of 10 μm or less [PM10], sulphur dioxide, nitrogen dioxide, and ozone) and a spatial statistical model (PM with an aerodynamic diameter of 1 μm or less [PM1] and 2·5 μm or less [PM2·5]). We used two-level logistic regression and linear regression analyses to assess associations between exposure and outcomes, controlling for confounders. Findings: All the studied pollutants were significantly associated with increased diabetes prevalence (eg, the adjusted odds ratios associated with an increase in IQR for PM1, PM2·5, and PM10 were 1·13, 95% CI 1·04–1·22; 1·14, 1·03–1·25; and 1·20, 1·12–1·28, respectively). These air pollutants were also associated with higher concentrations of fasting glucose (0·04–0·09 mmol/L), 2 h glucose (0·10–0·19 mmol/L), and 2 h insulin (0·70–2·74 μU/L). No association was observed for the remaining biomarkers. Stratified analyses indicated greater effects on the individuals who were younger (<50 years) or overweight or obese. Interpretation: Long-term exposure to air pollution was associated with increased risk of diabetes in a Chinese population, particularly in individuals who were younger or overweight or obese. Funding: The National Key Research and Development Program of China, the National Natural Science Foundation of China, the Fundamental Research Funds for the Central Universities, the Guangdong Province Natural Science Foundation, the Career Development Fellowship of Australian National Health and Medical Research Council, and the Early Career Fellowship of Australian National Health and Medical Research Council

Time to kick the butt of the most common litter item in the world: Ban cigarette filters

Cigarette filters offer no public health benefits, are single-use plastics (cellulose acetate) and are routinely littered. Filters account for a significant proportion of plastic litter worldwide, requiring considerable public funds to remove, and are a source of microplastics. Used cigarette filters can leech toxic chemicals and pose an ecological risk to both terrestrial and aquatic ecosystems. Bottom-up measures, such as focusing on consumer behaviour, are ineffective and we need to impose top-down solutions (i.e., bans) if we are to reduce the prevalence of this number one litter item. Banning filters offers numerous ecological, socioeconomic, and public health benefits

The time for ambitious action is now:Science-based recommendations for plastic chemicals to inform an effective global plastic treaty

The ubiquitous and global ecological footprint arising from the rapidly increasing rates of plastic production, use, and release into the environment is an important modern environmental issue. Of increasing concern are the risks associated with at least 16,000 chemicals present in plastics, some of which are known to be toxic, and which may leach out both during use and once exposed to environmental conditions, leading to environmental and human exposure. In response, the United Nations member states agreed to establish an international legally binding instrument on plastic pollution, the global plastics treaty. The resolution acknowledges that the treaty should prevent plastic pollution and its related impacts, that effective prevention requires consideration of the transboundary nature of plastic production, use and pollution, and that the full life cycle of plastics must be addressed. As a group of scientific experts and members of the Scientists' Coalition for an Effective Plastics Treaty, we concur that there are six essential “pillars” necessary to truly reduce plastic pollution and allow for chemical detoxification across the full life cycle of plastics. These include a plastic chemical reduction and simplification, safe and sustainable design of plastic chemicals, incentives for change, holistic approaches for alternatives, just transition and equitable interventions, and centering human rights. There is a critical need for scientifically informed and globally harmonized information, transparency, and traceability criteria to protect the environment and public health. The right to a clean, healthy, and sustainable environment must be upheld, and thus it is crucial that scientists, industry, and policy makers work in concert to create a future free from hazardous plastic contamination

Kollaborative, modulare Datenanalyse als Werkzeug im Qualitätsmanagement

ZusammenfassungIm Anwendungsfall zum datengetriebenen vernetzten Qualitätsmanagement im Forschungsprojekt AKKORD arbeiten Miele, IPS und RapidMiner an der Entwicklung eines modular erweiterbaren und ganzheitlichen Analysesystems auf Basis der im Projekt entwickelten Plattform. Inhaltlich wurden dafür Daten aus dem Bereich der Feldbeobachtung gewählt, die besonders interessant sind, da sie Rückschlüsse über die erlebte Qualität beim Kunden in der Nutzungsphase zulassen. Anhand von Ersatzteilverkäufen und anderen Datensätzen werden beispielhaft Analysebausteine zu Überwachung, Abweichungserkennung und Prognose erarbeitet. Durch die Übertragbarkeit der Analysebausteine und des Vorgehens auf sehr viele ähnliche Datenquellen kann so ein modularer Baukasten entstehen, der Transparenz über die aktuelle und zukünftige Qualitätssituation schafft. Die Erstellung der Analysebausteine durch Expertinnen und Experten aus dem Qualitätsmanagement anhand von Fragestellungen aus der Praxis wird durch ihre Befähigung auf dem Gebiet der Datenwissenschaften möglich. Dieses Kapitel beschreibt die Herangehensweise aus Sicht des Qualitätsmanagements, die Unterstützung, die AKKORD hinsichtlich der Problemstellung bietet sowie beispielhafte Ergebnisse und Analysebausteine des Anwendungsfalls im Rahmen des Forschungsprojekts.</jats:p