Induction of osteoclastogenesis in an in vitro model of Gaucher disease is mediated by T cells via TNF-α

Mucci, Juan Marcos; Scian, Romina; Francesco, Pablo N. De; García, Florencia Suqueli; Ceci, Romina; Fossati, Carlos A.; Delpino, M. Victoria; Rozenfeld, Paula

doi:10.1016/j.gene.2012.07.071

Cited by 32 publications

(41 citation statements)

References 46 publications

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“…The cellular alterations in GD produce a proinflammatory milieu mediated by proresorptive cytokines, such as TNF-␣, leading to bone destruction through enhancement of monocyte differentiation to osteoclasts and osteoclast resorption activity (97,124,128). GC modulates endolysosomal pH in lymphocytes, suggesting that this mechanism is disrupted in GD (84,158,162).…”

Section: Patients With Gaucher's Disease Before and After Enzyme Replmentioning

confidence: 99%

“…The PI3K/Akt signaling pathway in lipid rafts is relevant for insulin signaling (123,127). Cer blocks Akt activation, inhibiting Akt-dependent insulin signaling (124,163,167). There are conflicting results to the increased levels of Cer in humans with insulin resistance (24,25,34).…”

Section: Alteration Of Insulin Sensitivity In Patients With Gdmentioning

confidence: 99%

“…Oral administration of anti-LPS antibodies along with GSLenriched adjuvant compounds was effective in ameliorating NASH and diabetes in both animal models and humans (2,3,120,124,193,194). These effects were associated with alterations of Tregs and NKT cells, thereby supporting a potential effect of GSLs on the gut-microbiome-immune system axis.…”

Section: Effects Of Fxr Agonists and Anti-lps In Nash Are Partially Amentioning

confidence: 99%

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Compounds of the sphingomyelin-ceramide-glycosphingolipid pathways as secondary messenger molecules: new targets for novel therapies for fatty liver disease and insulin resistance

Ilan

2016

American Journal of Physiology-Gastrointestinal and Liver Physi

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The compounds of sphingomyelin-ceramide-glycosphingolipid pathways have been studied as potential secondary messenger molecules in various systems, along with liver function and insulin resistance. Secondary messenger molecules act directly or indirectly to affect cell organelles and intercellular interactions. Their potential role in the pathogenesis of steatohepatitis and diabetes has been suggested. Data samples collected from patients with Gaucher's disease, who had high levels of glucocerebroside, support a role for compounds from these pathways as a messenger molecules in the pathogenesis of fatty liver disease and diabetes. The present review summarizes some of the recent data on the role of glycosphingolipid molecules as messenger molecules in various physiological and pathological conditions, more specifically including insulin resistance and fatty liver disease.

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Section: Patients With Gaucher's Disease Before and After Enzyme Replmentioning

confidence: 99%

Section: Alteration Of Insulin Sensitivity In Patients With Gdmentioning

confidence: 99%

Section: Effects Of Fxr Agonists and Anti-lps In Nash Are Partially Amentioning

confidence: 99%

See 1 more Smart Citation

Compounds of the sphingomyelin-ceramide-glycosphingolipid pathways as secondary messenger molecules: new targets for novel therapies for fatty liver disease and insulin resistance

Ilan

2016

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…Moreover, we had previously shown that cellular alteration in GD, as modeled by in vitro GCase inhibition, produces bone destruction through the enhancement of macrophages differentiation to osteoclast and osteoclast resorption activity [18][19][20]. The aim of this study is to evaluate the presence and number of circulating proinflammatory cells and osteoclast precursors from Gaucher patients.…”

Section: Introductionmentioning

confidence: 99%

“…In bone loss-associated diseases, those osteoclast precursors are recruited from peripheral blood mononuclear cells (PBMCs) [16] and osteoclast formation occurs through stimulation by RANKL and macrophage colony-stimulating factor (M-CSF) [17][18][19]. In diseases with inflammatory conditions, osteoclastogenic cytokines necessary for osteoclast formation are produced by PBMCs themselves [16].…”

Section: Introductionmentioning

confidence: 99%

Proinflammatory and proosteoclastogenic potential of peripheral blood mononuclear cells from Gaucher patients: Implication for bone pathology

Mucci

Cuello

Kisinovsky³

et al. 2015

Blood Cells, Molecules, and Diseases

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MicroRNA‐23a modulates tumor necrosis factor‐alpha‐induced osteoblasts apoptosis by directly targeting fas

Dong

Cui

Jiang

et al. 2013

J of Cellular Biochemistry

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Tumor necrosis factor (TNF)-alpha is a key cytokine regulator of bone and mediates inflammatory bone loss. The molecular signaling that regulates bone loss downstream of TNF-alpha is poorly defined. Recent studies implicated an important role of microRNAs (miRNAs) in TNF-alpha-mediated bone metabolism, including osteoblasts differentiation, osteoclasts differentiation and apoptosis. However, there are very few studies on the complex regulation of miRNAs during TNF-alpha-induced osteoblasts apoptosis. In the present study, the clonal murine osteoblastic cell line, MC3T3-E1, was used. We screened for differentially expressed miRNAs during TNF-alpha induced MC3T3-E1 cell apoptosis and identified microRNA-23a as a potential inhibitor of apoptosis. To delineate the role of microRNA-23a in apoptosis, we respectively silenced and overexpressed microRNA-23a in MC3T3-E1 cells. We found that microRNA-23a depletion significantly enhances TNF-alpha-induced MC3T3-E1 cell apoptosis and over-expressing microRNA-23a remarkably attenuates this phenomenon. Mechanistic studies showed that microRNA-23a inhibits Fas expression through a microRNA-23a-binding site within the 3'-untranslational region of Fas. The post-transcriptional repression of Fas was further confirmed by luciferase reporter assay. These results showed that microRNA-23a, an important protecting factor, plays a significant role in the process of TNF-alpha induced MC3T3-E1 cell apoptosis, by regulating Fas expression.

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Induction of osteoclastogenesis in an in vitro model of Gaucher disease is mediated by T cells via TNF-α

Cited by 32 publications

References 46 publications

Compounds of the sphingomyelin-ceramide-glycosphingolipid pathways as secondary messenger molecules: new targets for novel therapies for fatty liver disease and insulin resistance

Compounds of the sphingomyelin-ceramide-glycosphingolipid pathways as secondary messenger molecules: new targets for novel therapies for fatty liver disease and insulin resistance

Proinflammatory and proosteoclastogenic potential of peripheral blood mononuclear cells from Gaucher patients: Implication for bone pathology

MicroRNA‐23a modulates tumor necrosis factor‐alpha‐induced osteoblasts apoptosis by directly targeting fas

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