Leptin receptor JAK2/STAT3 signaling modulates expression of Frizzled receptors in articular chondrocytes

SummaryObjectiveDifferentiated articular chondrocytes express a functional bisoform of the leptin receptor (LRb); however, leptin-LRb signaling in these cells is poorly understood. We hypothesized that leptin-LRb signaling in articular chondrocytes functions to modulate canonical Wnt signaling events by altering the expression of Frizzled (FZD) receptors.MethodsHuman chondrocyte cell lines and primary articular chondrocytes were grown in serum containing growth media for 24h, followed by a media change to Dulbecco’s modified Eagle’s medium (DMEM) containing 1% Nutridoma-SP to obtain a serum-deficient environment for 24h before treatment. Treatments included recombinant human leptin (10–100nM), recombinant human IL-6 (0.3–3nM), or recombinant human erythropoietin (Epo) (10mU/ml). Cells were harvested 30min–48h after treatment and whole cell lysates were analyzed using immunoblots or luciferase assays.ResultsTreatment of cells with leptin resulted in activation of Janus kinase 2 (JAK2) and subsequent phosphorylation of specific tyrosine residues on LRb, followed by dose- and time-dependent increases in the expression of Frizzled-1 (FZD1) and Frizzled-7 (FZD7). Leptin-mediated increases in the expression of FZD1 were blocked by pre-treatment with the protein synthesis inhibitor cycloheximide or the JAK2 inhibitor AG490. Experiments using a series of hybrid Epo extracellular domain-leptin intracellular domain receptors (ELR) harboring mutations of specific tyrosine residues in the cytoplasmic tail showed that increases in the expression of FZD1 were dependent on LRb-mediated phosphorylation of STAT3, but not ERK1/2 or STAT5. Leptin pre-treatment of chondrocytes prior to Wnt3a stimulation resulted in an increased magnitude of canonical Wnt signaling.ConclusionThese experiments show that leptin-LRb signaling in articular chondrocytes modulates expression of canonical Wnt signaling receptors and suggests that direct cross-talk between these pathways is important in determining chondrocyte homeostasis

Solutions to enteric methane abatement in Ireland

peer-reviewedThe efficiency of Ireland’s grass-based livestock systems can be attributed to high outputs, low production costs and a low carbon footprint relative to housed systems. Methane (CH4) is a potent greenhouse gas (GHG) of which enteric fermentation from livestock production is a key source, being directly responsible for 57% of Irish agricultural GHG emissions. There are a number of strategies including dietary manipulation and breeding initiatives that have shown promising results as potential mitigation solutions for ruminant livestock production. However, the majority of international research has predominantly been conducted on confined systems. Given the economic viability of Irish livestock systems, it is vital that any mitigation methods are assessed at pasture. Such research cannot be completed without access to suitable equipment for measuring CH4 emissions at grazing. This review documents the current knowledge capacity in Ireland (publications and projects) and includes an inventory of equipment currently available to conduct research. A number of strategic research avenues are identified herein that warrant further investigation including breeding initiatives and dietary manipulation. It was notable that enteric CH4 research seems to be lacking in Ireland as it constituted 14% of Irish agricultural GHG research publications from 2016 to 2021. A number of key infrastructural deficits were identified including respiration chambers (there are none currently operational in the Republic of Ireland) and an urgent need for more pasture-based GreenFeed™ systems. These deficits will need to be addressed to enable inventory refinement, research progression and the development of effective solutions to enteric CH4 abatement in Ireland

A review of evidence on the environmental impact of Ireland’s Rural Environment Protection Scheme (REPS)

peer-reviewedSince its inception in 1994, there has been strong demand for evidence of the environmental effectiveness of the Rural Environment Protection Scheme (REPS), which paid farmers in the Republic of Ireland over €3 billion by 2010. A variety of research projects have been undertaken that investigate the environmental effects of REPS through an examination of either specific environmental measures or specific geographical areas. A review of available publications confirmed the absence of a comprehensive, national-scale study of the environmental impacts of REPS. Because of this, there is insufficient evidence with which to judge the environmental effectiveness of the national-scale implementation of the whole scheme. For some specific measures, however, sufficient evidence is available to inform an objective assessment in some cases, and to help learn how to improve environmental effectiveness in most cases. The majority of the REPS payments are now dedicated toward biodiversity objectives. Thus, biodiversity measures and options should be a priority for any national-scale environmental assessment of the scheme. Such a study would help identify the environmental benefits of REPS, the specific elements of REPS that are performing adequately, and those elements that are in need of improvement. Given the considerable overlap between REPS measures and options and those included in the 2010 Agri-Environment Options Scheme (AEOS), assessment of REPS measures could also be used to inform the likely environmental performance of the AEOS