c-Fos induction by gut hormones and extracellular ATP in osteoblastic-like cell lines

Pacheco‐Pantoja, Elda; Dillon, J.P.; Wilson, Peter J.; Fraser, William D.; Gallagher, James A.

doi:10.1007/s11302-016-9526-3

Cited by 15 publications

(11 citation statements)

References 32 publications

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“…Therefore, ATP caused up‐regulation in 10% and down‐regulation in 11% of total glial transcriptome. Induction of genes, known to be expressed in direct response to ATP, including members of the regulator of calcineurin ( RCAN) (Canellada et al , 2008) and FOS (Pacheco‐Pantoja et al , 2016) gene families were confirmed by both RNA‐Seq and qPCR (Figs 1H and EV1D). Gene ontology (GO) enrichment analyses demonstrated a general glial activation in ATP‐treated msEGCs showing enriched genes for “ATP binding” and “glial proliferation” (Fig 1B and Appendix Fig B).…”

Section: Resultsmentioning

confidence: 78%

A novel P2X2‐dependent purinergic mechanism of enteric gliosis in intestinal inflammation

et al. 2020

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Enteric glial cells (EGC) modulate motility, maintain gut homeostasis, and contribute to neuroinflammation in intestinal diseases and motility disorders. Damage induces a reactive glial phenotype known as "gliosis", but the molecular identity of the inducing mechanism and triggers of "enteric gliosis" are poorly understood. We tested the hypothesis that surgical trauma during intestinal surgery triggers ATP release that drives enteric gliosis and inflammation leading to impaired motility in postoperative ileus (POI). ATP activation of a p38-dependent MAPK pathway triggers cytokine release and a gliosis phenotype in murine (and human) EGCs. Receptor antagonism and genetic depletion studies revealed P2X2 as the relevant ATP receptor and pharmacological screenings identified ambroxol as a novel P2X2 antagonist. Ambroxol prevented ATPinduced enteric gliosis, inflammation, and protected against dysmotility, while abrogating enteric gliosis in human intestine exposed to surgical trauma. We identified a novel pathogenic P2X2dependent pathway of ATP-induced enteric gliosis, inflammation and dysmotility in humans and mice. Interventions that block enteric glial P2X2 receptors during trauma may represent a novel therapy in treating POI and immune-driven intestinal motility disorders.

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Section: Resultsmentioning

confidence: 78%

A novel P2X2‐dependent purinergic mechanism of enteric gliosis in intestinal inflammation

et al. 2020

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“…In one study by Pancheco-Pantoja, GLP-1 increased cell viability and decreased P1NP secretion in two osteoblastic cell lines, TE-85, and MG-63 (20). In another study, they found that GLP-1 induces c-Fos expression (a gene important in bone cell proliferation and differentiation), in osteoblastic TE-85 cells, with a peak induction after 60 min (45). In mouse osteoblast-like MC3T3-E1 cells, the GLP-1RA, exendin-4, increased proliferation, differentiation, and mineralization through a MAPK pathway (47).…”

Section: The Gut-bone Axismentioning

confidence: 99%

“…GIP increases intracellular calcium [Ca 2+ ] i and cAMP, and increases expression of P1NP and ALP activity (30). It also increases the expression of c-Fos, an important factor in bone cell proliferation and differentiation (45). Furthermore, GIP improves collagen maturity and fibril diameter in a cAMP dependent manner (91), and stimulates both ALP and mineralization in primary osteoblast cultures from murine BMSC (34).…”

Section: The Gut-bone Axismentioning

confidence: 99%

Gut Hormones and Their Effect on Bone Metabolism. Potential Drug Therapies in Future Osteoporosis Treatment

et al. 2019

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Bone homeostasis displays a circadian rhythm with increased resorption during the night time as compared to day time, a difference that seems—at least partly—to be caused by food intake during the day. Thus, ingestion of a meal results in a decrease in bone resorption, but people suffering from short bowel syndrome lack this response. Gut hormones, released in response to a meal, contribute to this link between the gut and bone metabolism. The responsible hormones appear to include glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), known as incretin hormones due to their role in regulating glucose homeostasis by enhancing insulin release in response to food intake. They interact with their cognate receptors (GIPR and GLP-1R), which are both members of the class B G protein-coupled receptors (GPCRs), and already recognized as targets for treatment of metabolic diseases, such as type 2 diabetes mellitus (T2DM) and obesity. Glucagon-like peptide-2 (GLP-2), secreted concomitantly with GLP-1, acting via another class B receptor (GLP-2R), is also part of this gut-bone axis. Several studies, including human studies, have indicated that these three hormones inhibit bone resorption and, moreover, that GIP increases bone formation. Another hormone, peptide YY (PYY), is also secreted from the enteroendocrine L-cells (together with GLP-1 and GLP-2), and acts mainly via interaction with the class A GPCR NPY-R2. PYY is best known for its effect on appetite regulation, but recent studies have also shown an effect of PYY on bone metabolism. The aim of this review is to summarize the current knowledge of the actions of GIP, GLP-1, GLP-2, and PYY on bone metabolism, and to discuss future therapies targeting these receptors for the treatment of osteoporosis.

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“…There are other possible pathways by which GLP-1 could affect bone formation. It has been proposed that GLP-1 could promote c-Fos transcription in osteoblasts in combination with ATP, facilitating the participation of GLP-1 in bone turnover ( 47 ). It has been shown that exendin-4 enhanced the proliferation and differentiation of osteoblasts partly mediated by MAPK pathways, including ERK1/2, p38, and JNK pathways ( 48 ).…”

Section: The Potential Mechanisms Of the Glp-1 Effects On Bone Metabomentioning

confidence: 99%

The Impact of Glucagon-Like Peptide-1 on Bone Metabolism and Its Possible Mechanisms

et al. 2017

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The impact of antidiabetic drugs on bone metabolism is drawing increasing attention due to the discovery of a correlation between type 2 diabetes mellitus (T2DM) and osteoporosis. Glucagon-like peptide-1 (GLP-1) receptor agonists are a novel and promising class of drugs for T2DM, which may also have clinical applications in bone tissue disorders. This review examines the impact of GLP-1 on bone metabolism, including enhancement of bone mineral density and improvement of bone quality. However, the precise effect of GLP-1 on fracture risk has not been unambiguously defined. This review also summarizes our current understanding of the mechanisms by which GLP-1 affects bone metabolism. GLP-1 may act on bone by promoting bone formation, inhibiting bone resorption, and affecting the coordination of the two processes. We describe molecular pathways and proteins, such as Wnt and calcitonin, that are associated with GLP-1 and bone tissue. The specific processes and related molecular mechanisms of the effects of GLP-1 on bone metabolism need to be further explored and clarified.

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c-Fos induction by gut hormones and extracellular ATP in osteoblastic-like cell lines

Cited by 15 publications

References 32 publications

A novel P2X2‐dependent purinergic mechanism of enteric gliosis in intestinal inflammation

A novel P2X2‐dependent purinergic mechanism of enteric gliosis in intestinal inflammation

Gut Hormones and Their Effect on Bone Metabolism. Potential Drug Therapies in Future Osteoporosis Treatment

The Impact of Glucagon-Like Peptide-1 on Bone Metabolism and Its Possible Mechanisms

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