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Spontaneous generation of functional osteoclasts from synovial fluid mononuclear cells as a model of inflammatory osteoclastogenesis
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Stinne R. Greisen Halldór Bjarki Einarsson Malene Hvid Ellen‐Margrethe Hauge Bent Deleuran Tue Wenzel Kragstrup 《APMIS : acta pathologica, microbiologica, et immunologica Scandinavica》2015,123(9):779-786
In osteoimmunology, osteoclastogenesis is understood in the context of the immune system. Today, the in vitro model for osteoclastogenesis necessitates the addition of recombinant human receptor activator of nuclear factor kappa‐B ligand (RANKL) and macrophage colony‐stimulating factor (M‐CSF). The peripheral joints of patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA) are characterized by an immune‐mediated inflammation that can lead to bone destruction. Here, we evaluate spontaneous in vitro osteoclastogenesis in cultures of synovial fluid mononuclear cells (SFMCs) activated only in vivo. SFMCs were isolated and cultured for 21 days at 0.5–1.0 × 106 cells/mL in culture medium. SFMCs and healthy control peripheral blood monocytes were cultured with RANKL and M‐CSF as controls. Tartrate‐resistant acid phosphatase (TRAP) positive multinucleated cells were found in the SFMC cultures after 21 days. These cells expressed the osteoclast genes calcitonin receptor, cathepsin K, and integrin β3, formed lacunae on dentin plates and secreted matrix metalloproteinase 9 (MMP9) and TRAP. Adding RANKL and M‐CSF potentiated this secretion. In conclusion, we show that SFMCs from inflamed peripheral joints can spontaneously develop into functionally active osteoclasts ex vivo. Our study provides a simple in vitro model for studying inflammatory osteoclastogenesis. 相似文献
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David M. Presby Michael C. Rudolph Vanessa D. Sherk Matthew R. Jackman Rebecca M. Foright Kenneth L. Jones Julie A. Houck Ginger C. Johnson Janine A. Higgins P. Darrell Neufer Robert H. Eckel Paul S. MacLean 《Diabetes》2021,70(4):867
Moderate weight loss improves numerous risk factors for cardiometabolic disease; however, long-term weight loss maintenance (WLM) is often thwarted by metabolic adaptations that suppress energy expenditure and facilitate weight regain. Skeletal muscle has a prominent role in energy homeostasis; therefore, we investigated the effect of WLM and weight regain on skeletal muscle in rodents. In skeletal muscle of obesity-prone rats, WLM reduced fat oxidative capacity and downregulated genes involved in fat metabolism. Interestingly, even after weight was regained, genes involved in fat metabolism were also reduced. We then subjected mice with skeletal muscle lipoprotein lipase overexpression (mCK-hLPL), which augments fat metabolism, to WLM and weight regain and found that mCK-hLPL attenuates weight regain by potentiating energy expenditure. Irrespective of genotype, weight regain suppressed dietary fat oxidation and downregulated genes involved in fat metabolism in skeletal muscle. However, mCK-hLPL mice oxidized more fat throughout weight regain and had greater expression of genes involved in fat metabolism and lower expression of genes involved in carbohydrate metabolism during WLM and regain. In summary, these results suggest that skeletal muscle fat oxidation is reduced during WLM and regain, and therapies that improve skeletal muscle fat metabolism may attenuate rapid weight regain. 相似文献
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Neurofibromatosis Type 1 Diagnosed in a Child Based on Multiple Juvenile Xanthogranulomas and Juvenile Myelomonocytic Leukemia
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Sune R. R. Jans M.D. Eckhard Schomerus M.D. Anette Bygum M.D. 《Pediatric dermatology》2015,32(1):e29-e32
An association between juvenile xanthogranuloma (JXG), neurofibromatosis type 1 (NF1), and juvenile myelomonocytic leukemia (JMML) has been described in the literature but has only been documented in approximately 20 cases. We diagnosed a patient with NF1 at 25 months of age, before any cutaneous stigmata of this disease had appeared, because we decided to screen for the NF1 gene mutation because of his presentation with multiple JXGs and moderate macrocephaly (2.5 standard deviations) at 9 months of age and JMML diagnosed at 20 months of age. The child is well today after treatment with chemotherapy and allogenic bone marrow transplantation. With increased awareness, patients with JXG and NF1 who develop symptoms possibly related to JMML, such as paleness, skin bleeding, cough, unexplained fever, and hepatosplenomegaly, should be further evaluated. We also emphasize that multiple JXG lesions can be an early marker of NF1. 相似文献
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R. E. J. Ryder 《Diabetic medicine》2015,32(3):305-313
On 8 April 2014, a US jury ordered Takeda and Eli Lilly to pay $9 bn in punitive damages after finding that they had concealed the cancer risks associated with pioglitazone. By contrast, on 28 August 2014, the long‐awaited outcome of the 10‐year Kaiser Permanente Northern California study was announced. That study was specifically designed to investigate whether patients exposed to pioglitazone were at an increased risk of bladder cancer and found no association; thus, at last, the controversial issue has been resolved. A review, in retrospect, of the story of the proposed link between pioglitazone and bladder cancer reveals flaws at every stage. In 2012, a BMJ editorial, in keeping with some other contemporary reports, stated ‘it can confidently be assumed that pioglitazone increases the risk of bladder cancer’. Examination of the information which led to such a statement shows that: 1) the pre‐clinical findings of bladder cancer in male rats is not indicative of human risk; 2) there is no association between bladder cancer and pioglitazone in randomized controlled trials, once cases that could not plausibly be related to treatment are removed; and 3) the observational studies that have suggested a link have over‐extrapolated from the data: pioglitazone‐treated patients had more risk factors for bladder cancer than those not treated with pioglitazone. Meanwhile careful study of randomized controlled trials shows evidence of cardiovascular benefit from pioglitazone in Type 2 diabetes, a condition which results, more than anything, in premature cardiovascular death and morbidity. 相似文献