68 research outputs found
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 P2X7â/â (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
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
Extracellular ATP released by osteoblasts is a key local inhibitor of bone mineralisation
Previous studies have shown that exogenous ATP (>1”M) 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 (â€25%) in osteoblast number, suggesting a role for endogenous ATP in stimulating cell proliferation. Continuous apyrase treatment for 14 days (â„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
Risk Perception of Plastic Pollution: Importance of Stakeholder Involvement and Citizen Science
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
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 15â477 participants aged 18â74 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 ÎČ-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 ÎŒm or less [PM10], sulphur dioxide, nitrogen dioxide, and ozone) and a spatial statistical model (PM with an aerodynamic diameter of 1 ÎŒm or less [PM1] and 2·5 ÎŒm 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 1·04â1·22; 1·14, 1·03â1·25; and 1·20, 1·12â1·28, respectively). These air pollutants were also associated with higher concentrations of fasting glucose (0·04â0·09 mmol/L), 2 h glucose (0·10â0·19 mmol/L), and 2 h insulin (0·70â2·74 ÎŒU/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
Moving from symptom management to upstream plastics prevention: The fallacy of plastic cleanup technology
Plastic removal technologies can temporarily mitigate plastic accumulation at local scales, but evidence-based criteria are needed in policies to ensure that they are feasible and that ecological benefits outweigh the costs. To reduce plastic pollution efficiently and economically, policy should prioritize regulating and reducing upstream production rather than downstream pollution cleanup
Aquatic Ecotoxicity of Microplastics and Nanoplastics: Lessons Learned from Engineered Nanomaterials
Creating positive environmental impact through citizen science
Interest in citizen science is growing, including from governments and research funders. This interest is often driven by a desire for positive environmental impact, and the expectation that citizen science can deliver it by engaging the public and simultaneously collecting environmental data. Yet, in practice, there is often a gap between expected and realised impact. To close this gap, we need to better understand pathways to impact and what it takes to realise them. We articulate six key pathways through which citizen science can create positive environmental change: (1) environmental management; (2) evidence for policy; (3) behaviour change; (4) social network championing; (5) political advocacy; and (6) community action. We explore the project attributes likely to create impact through each of these pathways and show that there is an interplay between these project attributes and the needs and motivations of target participant groups. Exploring this interplay, we create a framework that articulates four citizen science approaches that create environmental impact in different ways: place-based community action; interest group investigation; captive learning research; and mass participation census
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