Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Insulin receptor signaling in osteoblasts regulates postnatal bone acquisition and body composition

ABSTRACT: Global energy balance in mammals is controlled by the actions of circulating hormones that coordinate fuel production and utilization in metabolically active tissues. Bone-derived osteocalcin, in its undercarboxylated, hormonal form, regulates fat deposition and is a potent insulin secretagogue. Here, we show that insulin receptor (IR) signaling in osteoblasts controls osteoblast development and osteocalcin expression by suppressing the Runx2 inhibitor Twist-2. Mice lacking IR in osteoblasts have low circulating undercarboxylated osteocalcin and reduced bone acquisition due to decreased bone formation and deficient numbers of osteoblasts. With age, these mice develop marked peripheral adiposity and hyperglycemia accompanied by severe glucose intolerance and insulin resistance. The metabolic abnormalities in these mice are improved by infusion of exogenous under-carboxylated osteocalcin. These results indicate the existence of a bone-pancreas endocrine loop through which insulin signaling in the osteoblast ensures osteoblast differentiation and stimulates osteocalcin production, which in turn regulates insulin sensitivity and pancreatic insulin secretion to control glucose homeostasis. We used microarrays to detail the global gene expression changes in response to insulin acting through insulin receptor in osteoblasts and identified distinct genes specifically involved in bone remodeling process.

ORGANISM(S): Mus musculus

PROVIDER: GSE21710 | GEO | 2010/05/07

SECONDARY ACCESSION(S): PRJNA127163

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Insulin receptor signaling in osteoblasts regulates postnatal bone acquisition and body composition

Project description:Global energy balance in mammals is controlled by the actions of circulating hormones that coordinate fuel production and utilization in metabolically active tissues. Bone-derived osteocalcin, in its undercarboxylated, hormonal form, regulates fat deposition and is a potent insulin secretagogue. Here, we show that insulin receptor (IR) signaling in osteoblasts controls osteoblast development and osteocalcin expression by suppressing the Runx2 inhibitor Twist-2. Mice lacking IR in osteoblasts have low circulating undercarboxylated osteocalcin and reduced bone acquisition due to decreased bone formation and deficient numbers of osteoblasts. With age, these mice develop marked peripheral adiposity and hyperglycemia accompanied by severe glucose intolerance and insulin resistance. The metabolic abnormalities in these mice are improved by infusion of exogenous under-carboxylated osteocalcin. These results indicate the existence of a bone-pancreas endocrine loop through which insulin signaling in the osteoblast ensures osteoblast differentiation and stimulates osteocalcin production, which in turn regulates insulin sensitivity and pancreatic insulin secretion to control glucose homeostasis. We used microarrays to detail the global gene expression changes in response to insulin acting through insulin receptor in osteoblasts and identified distinct genes specifically involved in bone remodeling process. 4 groups and 3 time points (0h as a control, 6h, 12h, and 24h)

2010-05-27 | E-GEOD-21710 | biostudies-arrayexpress

Low-density lipoprotein receptor-5 contributes to whole body metabolism by regulating fatty acid metabolism in the osteoblast

Project description:Wnt signaling is critical for normal skeletal development as well as whole-body metabolic function. In this study, we described a previously unrecognized function for Wnt-Lrp5 signaling in the osteoblast that allows bone to acquire the resources necessary to fuel bone formation. Mice lacking the Lrp5 co-receptor specifically in osteoblasts and osteocytes exhibit the expected reductions in postnatal bone mass and also develop peripheral adiposity with corresponding reductions in energy expenditure. Conversely, mice expressing a high-bone mass mutant Lrp5 allele are leaner with reduced plasma triglyceride and free fatty acid levels. In this context, Wnt-initiated signals downstream of Lrp5, but not Lrp6, regulate the expression of key enzymes required for fatty acid β-oxidation. These results suggest that Wnt-Lrp5 signaling regulates basic cellular activities beyond those associated with fate-specification and differentiation in bone and that the skeleton influences global energy homeostasis via mechanisms independent of osteocalcin and glucose metabolism Total RNA isolated from cultures of Lrp5-deficient osteoblasts differentiated for 7 days in vitro compared to control osteoblasts

2014-03-14 | E-GEOD-55900 | biostudies-arrayexpress

Genetic activation of glycolysis in osteoblasts preserves bone mass in type I diabetes [bulkRNA-seq]

Project description:Type I diabetes (T1D) impairs bone accrual in patients, but the mechanism is unclear. Here in a murine monogenic model for T1D, we demonstrate that diabetes suppresses bone formation resulting in a rapid loss of both cortical and trabecular bone. Single-cell RNA sequencing uncovers metabolic dysregulation in bone marrow osteogenic cells of the diabetic mice. In vivo stable isotope tracing reveals impaired glycolysis in diabetic bone that is highly responsive to insulin stimulation. Remarkably, deletion of the insulin receptor reduces cortical but not trabecular bone. Increasing glucose uptake by overexpressing Glut1 in osteoblasts exacerbates bone defects in T1D mice. Conversely, activation of glycolysis by Pfkfb3 overexpression preserves both trabecular and cortical bone mass in the face of diabetes. The study identifies defective glucose metabolism in osteoblasts as a pathogenic mechanism for osteopenia in T1D, and furthermore implicates boosting osteoblast glycolysis as a potential anabolic therapy.

2023-06-20 | GSE232736 | GEO

Genetic activation of glycolysis in osteoblasts preserves bone mass in type I diabetes [scRNA-seq]

2023-06-20 | GSE232737 | GEO

Low-density lipoprotein receptor-5 contributes to whole body metabolism by regulating fatty acid metabolism in the osteoblast

2014-03-14 | GSE55900 | GEO

Expression data from NPY Y1R-deficient osteoblastic cells

Project description:NPY signalling via osteoblastic Y1 receptors has been shown to control bone mass but also contributes significantly to the control of whole-body insulin secretion and glucose homeostasis in mice through the release of novel factor(s) which are different from the previously implicated osteocalcin. We used microarrays to identify novel endocrine factors regulated by Y1 receptors and involved in the regulation of bone mass and whole-body homeostasis.

2018-05-16 | GSE114469 | GEO

Intercellular communication via miR-143-containing microvesicles controls osteoblastic bone formation in vivo

Project description:Osteoblasts are the only somatic cell type with bone-forming ability. While the cellular and molecular mechanisms underlying their differentiation and function have been identified, their dynamic control in vivo is unclear. By intravital multiphoton microscopy of live bone tissues of osteoblast fluorescent reporter mice, we visualized intact mature osteoblasts in vivo and found that they actively secrete and capture extracellular microvesicles. Microvesicles from mature osteoblasts contain the microRNA miR-143-3p, which inhibits osteoblast differentiation. Osteoblast-specific deletion of miR-143 increased bone formation and miR-143-deficient microvesicles induced recovery from bone defect. In sum, we report a novel mode of intercellular communication in vivo via microRNA-containing extracellular vesicles, which controls bone homeostasis.

2022-02-04 | GSE144512 | GEO

Skeletal glucocorticoid signaling determines aging-related leptin resistance and obesity

Project description:Aging contributes to many chronic conditions, including central obesity, insulin resistance and osteoporosis, which are also critical features of glucocorticoid excess. To investigate tissue-specific sites of glucocorticoid (GC) action during aging, we disrupted GC signalling in mouse osteoblasts via transgenic overexpression of the GC-inactivating enzyme, 11β-hydroxysteroid-dehydrogenase type 2 (11β-HSD2). Wild-type mice with intact osteoblastic GC signalling developed leptin resistance, obesity and insulin resistance with aging. In contrast, transgenic (HSD2OB-tg) mice remained lean and leptin-sensitive, and were protected against aging-related hyperinsulinaemia, blunted sympathetic responses and loss of thermogenic adipose tissue. These salutary effects were independent of the osteoblast-derived factors osteocalcin and lipocalin-2. Gene expression analysis of bones from HSD2OB-tg mice indicated an early induction of pro-osteogenic and anti-adipogenic factors, and activation of a local pro-inflammatory TLR4-ZBTB16-NR1H3 network in osteoblastic cells. These findings reveal a critical role for skeletal glucocorticoid signaling in central leptin action, and in impaired metabolic function with aging

2020-11-09 | GSE141448 | GEO

The long noncoding RNA lnc-ob1 facilitates bone formation by upregulating Osterix in osteoblasts

Project description:Long noncoding RNAs (lncRNAs) have emerged as integral regulators of physiology and disease, but specific roles of lncRNAs in bone disease remain largely unknown. Here, we show that lnc-ob1 regulates osteoblast activity and bone formation in mice by upregulating the osteogenic transcription factor Osterix. Expression of lnc-ob1 is enriched in osteoblasts and upregulated during osteoblastogenesis. We demonstrate that osteoblast-specific knock-in of lnc-ob1 enhances bone formation and increases bone mass. Pharmacological overexpression of lnc-ob1 specifically in osteoblasts confers resistance to ovariectomy-induced osteoporosis in mice. In humans, expression of the homologue, lnc-OB1, decreases with age in osteoblasts of patients with osteoporosis. Mechanistically, lnc-ob1 upregulates the expression of Osterix in mouse and human osteoblasts, probably via inhibition of H3K27me3 methylation. Our data indicate that lnc-OB1 regulates bone formation and might be a drug target for the treatment of osteoporosis.

2019-03-28 | GSE112318 | GEO

Mechanical force promotes dimethylarginine dimethylaminohydrolase 1-mediated hydrolysis of the metabolite asymmetric dimethylarginine to enhance bone formation

Project description:<p>Mechanical force is critical for the development and remodeling of bone. Here we report that mechanical force regulates the production of the metabolite asymmetric dimethylarginine (ADMA) via regulating the hydrolytic enzyme dimethylarginine dimethylaminohydrolase 1 (Ddah1) expression in osteoblasts. The presence of -394 4N del/ins polymorphism of Ddah1 and higher serum ADMA concentration are negatively associated with bone mineral density. Global or osteoblast-specific deletion of Ddah1 leads to increased ADMA level but reduced bone formation. Further molecular study unveils that mechanical stimulation enhances TAZ/SMAD4-induced Ddah1 transcription. Deletion of Ddah1 in osteoblast-lineage cells fails to respond to mechanical stimulus-associated bone formation. Taken together, the study reveals mechanical force is capable of down-regulating ADMA to enhance bone formation.</p>

2021-11-23 | MTBLS3725 | MetaboLights

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data