Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The orally available SIK2/SIK3 inhibitor SK-124 increases bone mass in hypogonadal male mice

ABSTRACT: We previously described the synthesis and characterization of SK-124, a pharmacologic SIK2/SIK3 inhibitor that increases trabecular bone formation in eugonadal mice. However, the efficacy of this agent in osteoporosis mouse models remains unknown. In this study, we investigated the therapeutic potential of SK-124 in a male hypogonadal bone loss model (orchiectomy, ORX) in BALB/c male mice.Bone RNA-sequencing analysis demonstrated novel pathways associated with increased bone formation in response to SK-124 treatment.

ORGANISM(S): Mus musculus

PROVIDER: GSE310090 | GEO | 2026/03/31

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

The orally available SIK2/SIK3 inhibitor SK-124 increases bone mass in hypogonadal male mice

Project description:The orally available SIK2/SIK3 inhibitor SK-124 increases bone mass in hypogonadal male mice

| PRJNA1365103 | ENA

The SIK2/SIK3 inhibitor GLPG3970 increases bone formation and trabecular bone mass in hypogonadal female mice and rats

Project description:Currently, there are no orally available bone anabolic therapies to treat osteoporosis. Intermittent parathyroid hormone injections stimulate bone formation through a signaling pathway that inhibits the actions of salt inducible kinase (SIK) isoforms 2 and 3. Therefore, direct small molecule SIK2/SIK3 inhibitors represent a promising treatment strategy to mimic PTH actions. Here we tested GLPG3970, a potent and selective SIK2/SIK3 inhibitor developed for clinical use in inflammatory diseases, in rodent models of post-menopausal osteoporosis. In bone cells, GLPG3970 reduces phosphorylation levels of SIK substrates and regulates gene expression patterns, as assessed by RNA-sequencing, in a PTH-like manner. GLPG3970 was administered to female mice and rats rendered hypogonadal via surgical oophorectomy (OVX) via twice daily oral gavage. In parallel, separate groups of rodents were treated with once daily subcutaneous PTH injections. Skeletal endpoints, serum bone turnover markers, micro-CT, histomorphometry, and mechanical testing, were assessed after study termination. In both OVX-operated mice and rats, GLPG3970 treatment increased markers of bone formation and cancellous bone mass, and increased rat vertebral body bone strength. These results provide strong justification for further development of orally available SIK2/SIK3 inhibitors to treat post-menopausal osteoporosis.

2025-09-01 | GSE285777 | GEO

The SIK2/SIK3 inhibitor GLPG3970 increases bone formation and trabecular bone mass in hypogonadal female mice and rats

Project description:The SIK2/SIK3 inhibitor GLPG3970 increases bone formation and trabecular bone mass in hypogonadal female mice and rats

| PRJNA1206073 | ENA

Genome-wide analysis of SIK2 regulated genes and pathways

Project description:Identification of SIK2 regulated genes and pathways after SIK2 knock-down and overexpression of a wild-type and kinase-dead SIK2. The hypothesis is that SIK2 regulated gene expression via CREB1 Total RNAs were obtained after SIK2 gene was knocked down with siRNA and after a wild-type SIK2 or a kinase-dead SIK2 construct were over-expressed in LNCaP cells. A control where the cells were treated with a CREB1 inducer (Forskolin) was also included.

2015-01-12 | E-GEOD-45711 | biostudies-arrayexpress

Hypogonadal mice and testosterone proprionate treatment

Project description:Analysis of the transcriptome of testes of hypogonadal mice that had been pretreated with testosterone proprionate for 2 weeks then submitted to testosterone withdrawal. Keywords = testis, hypogonadal mice, testosterone Keywords: other

2003-05-28 | GSE438 | GEO

Genome-wide analysis of SIK2 regulated genes and pathways

2015-01-12 | GSE45711 | GEO

Inhibition of Salt-Inducible Kinases 2 and 3 reduces inflammatory signature in Psoriasis

Project description:Psoriasis is a highly prevalent inflammatory skin disease for which good systemic therapeutic agents are available. However, there still is a great need for new treatment options, especially oral ones. Salt-inducible kinases (SIKs) are emerging as new druggable targets in immune diseases and the SIK2/SIK3 inhibitor GLPG3970 recently proved to efficiently reduce psoriasis lesions in a phase Ib trial. This study assesses molecular events underlying beneficial effects of SIK2/SIK3 inhibition via GLPG3970 in psoriasis. Using spatial transcriptomics and single cell sequencing, abundant expression of SIK2 and SIK3, but not of SIK1, was observed in psoriatic skin. In vitro, GLPG3970 reduced psoriasis marker cytokines and chemokines (TNF, IFN-, IL-1, IL-6, CXCL8, CXCL10) in peripheral mononuclear cells, T cells and fibroblasts, but not in keratinocytes. Bulk RNA sequencing of lesional psoriasis biopsies treated ex vivo with GLPG3970 and of biopsies received from responders vs. placebo-treated patients of the clinical trial showed downregulation of inflammatory pathways with suppression of IL1B, CXCL1, CXCL8, CEBPB, CD177, and CLEC5A in both settings. In summary, this study suggests that specific inhibition of SIK2/SIK3 reduces acute phase immunity and neutrophil recruitment in psoriasis.

2026-05-20 | GSE331382 | GEO

Hypothalamic astrocytes TRAP-seq in ORX/HFD mice

Project description:3' mRNA-sequencing of the immunoprecipitated and supernatant fractions after Translating Ribosome Affinity Purification (TRAP) targeted to hypothalamic astrocytes RNA (from Aldh1l1eGFP-L10a mice) for 3 experimental conditions: chow diet; high-fat diet; high-fat diet + orchiectomy (Sham-chow n=7, Sham-HFD n=6, ORX-HFD n=7)

2023-04-03 | GSE214683 | GEO

SIK2-dependent Phosphoproteome and Interactome upon Salmonella infection

Project description:HeLa cells transfected with non-targeting control- and anti-SIK2 siRNA were left uninfected or infected with Salmonella and lysed 30 min pi. Following tryptic-digest peptides were labeled using TMT-pro 16-plex and phosphopeptides enriched. The endogenously tagged SIK2-HA IP workflow. Hela wild type or endogenous SIK2-HA-tagged HeLa cells were left uninfected or infected with Salmonella and lysed 1 h post-infection, followed by HA-IP, Tryptic digest, TMT-labeling and LC-MS/MS analysis.

2021-05-06 | PXD021859 | Pride

LKB1-SIK2 loss drives uveal melanoma proliferation and hypersensitivity to SLC8A1 and ROS inhibition

Project description:Metastatic uveal melanomas are highly resistant to all existing treatments. To address this critical issue, we performed a genome-wide CRISPR-Cas9 knockout screen, which revealed the LKB1-SIK2 module in restraining uveal melanoma tumorigenesis. Functionally, LKB1 loss enhances proliferation and survival through SIK2 inhibition and up-regulation of the sodium/calcium (Na+/Ca2+) exchanger SLC8A1. This signalling cascade promotes increased level of intracellular calcium and mitochondrial reactive oxygen species, two hallmarks of cancer. We further demonstrate that combination of an SLC8A1 inhibitor and a mitochondria-targeted antioxidant promotes enhanced cell death efficacy in LKB1- and SIK2-negative uveal melanoma cells compared to control cells. We also designed an LKB1-deficient prognostic gene signature of patient survival that may be predictive of response to this combination. Our data thus identify not only metabolic vulnerabilities, but also new prognostic markers, thereby providing a therapeutic strategy for particular subtypes of metastatic uveal melanoma.

2024-05-25 | GSE233458 | GEO

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