Effect of BMS-582949 treatment on gene expression in osteoclasts
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE249860 | GEO | 2024/02/29
REPOSITORIES: GEO
Similar Datasets
Project description:Apical periodontitis (AP) is an inflammatory disease occurring following tooth infection with distinct osteolytic activity. Despite increasing evidence that sensory neurons participate in regulation of non-neuronal cells, their role in the development of AP is largely unknown. We hypothesized that Nav1.8+ nociceptors regulate bone metabolism changes in response to AP. Methods: A selective ablation of nociceptive neurons in Nav1.8Cre/ DTALox mouse line was used to evaluate the development and progression of AP using murine model of infection-induced AP. Micro-computed tomography examination was applied to quantify osteolytic lesions following induction of AP. Additionally, RT-PCR, RNAscope, and immunohistochemical (IHC) analysis were used to investigate the expression of immune cells, osteoblasts, and osteoclasts. Co-culture of trigeminal ganglia (TG) neurons from DTALox (control) and Nav1.8Cre/ DTALox mice with either IDG-SW3 or MC3T3-E1 osteoblast precursor cell lines or RAW264.7 murine macrophages were used to assess osteoblast and osteoclast function, by RNA sequencing, mineralization, and osteoclastic assays. Results: Ablation of Nav1.8+ nociceptors had earlier progression of AP with larger osteolytic lesions compared to the controls. IHC and RNAscope analysis demonstrated greater number of macrophages, T-cells, osteoclast and osteoblast precursors as well as an increased RANKL:OPG ratio at earlier time points among Nav1.8Cre/ DTALox mice. There was an increased expression of IL-1a and IL-6 within lesions of nociceptor-ablated mice. Further, co-culture experiments demonstrated that TG neurons promoted osteoblast mineralization and inhibited osteoclastic function. Conclusion: The findings suggest that TG Nav1.8+ neurons contribute to modulation of the AP development by delaying the influx of immune cells, promoting osteoblastic differentiation, and decreasing osteoclastic activities. This newly uncovered mechanism could become a therapeutic strategy for the treatment of AP and minimize the persistence of osteolytic lesions in refractory cases.
2022-09-01 | GSE198091 | GEO
Project description:Estrogen clearly prevents osteoporotic bone loss by attenuating bone resorption. The molecular basis of how this is accomplished, however, remains elusive. Here we report a critical role of osteoclastic ERa in mediating estrogen action on bone in females. We selectively ablated ERa in differentiated osteoclasts (ERa dOc/dOc). ERa dOc/dOc females, but not males, exhibited clear trabecular bone loss, similar to the osteoporotic bone phenotype in post-menopausal women. Recovery of bone loss by estrogen treatment of the ovariectomized ERa dOc/dOc females was ineffective in the trabecular areas of the long bones and lumbar vertebral bodies. Osteoclastic apoptosis, induced by estrogen, occurred simultaneously with up-regulation of Fas ligand (FasL) expression in intact trabecular bones of ERa +/+mice, but not in ERa dOc/dOc mice. ERa was also required for similar effects of estrogen and tamoxifen in cultured osteoclasts. These findings suggest that the osteoprotective actions of estrogen and SERMS are mediated at least in part through osteoclastic ERa in trabecular bone; and the life span of mature osteoclasts is regulated through activation of the Fas/FasL system. Experiment Overall Design: Wild type and osteoclast-specific Estrogen Receptor alpha knock-out mice were ovariectomized. The number of both genotypes of mice was eight. The mice of each genotypes were divided to vehicle control and estrogen treated group. Four hours after chemical treatment, the distal 5 mm of the left femurs were harvested after sacrificing by cervical dislocation and total RNAs were purified for Affymetix GeneChip microarray analysis without pooling. Therefore, this experiment consists of four groups with four replicates per group.
2008-06-15 | E-GEOD-7798 | biostudies-arrayexpress
Project description:Def6 suppresses osteoblast differentiation and mineralization both in vitro and in vivo. Def6 knockout (KO) mice exhibit osteoporotic phenotype with enhanced osteoclast formation. Osteoblast differentiation and bone formation are elevated as well in Def6 KO mice, indicating a high bone turnover rate that leads to bone loss in Def6 KO mice. Thus, lack of Def6 leads towards unbalanced activities between osteoclastic resorption and osteoblast mediated bone formation and disrupts normal bone remodeling. Def6 suppresses osteoblast differentiation via endogenous type I IFN-mediated feedback inhibition. These findings reveal that Def6 is a novel bone remodeling regulator that controls both osteoclast and osteoblast differentiation to maintain bone remodeling.
2021-01-04 | GSE148455 | GEO
Project description:CST6 suppresses osteolytic bone disease in multiple myeloma by blocking osteoclast differentiation
| PRJNA791247 | ENA
Project description:Maintenance of bone homeostasis and the balance between bone resorption and formation are crucial for maintaining skeletal integrity. Osteoclasts are responsible for bone resorption and play a vital role in this process. The role of salt-inducible kinase 3 (SIK3) in osteoclast differentiation and maturation and its potential as a therapeutic target for osteoporosis remain poorly understood. Here, we generated osteoclast-specific Sik3 conditional knockout (cKO) mice and investigated the effects of SIK3 deletion on bone homeostasis. Our findings revealed increased bone mineral density and an osteopetrosis phenotype in Sik3 cKO mice, indicating the involvement of SIK3 in bone resorption. Furthermore, we examined the effect of pterosin B, an SIK3 inhibitor, on osteoclast differentiation. Pterosin B treatment inhibits osteoclast differentiation in vitro, reduces the number of multinucleated osteoclasts, and suppresses bone resorption. Therefore, in this study, to better understand the molecular mechanism of SIK3 in osteoclast differentiation and maturation, we performed gene expression profiling of bone marrow monocytes from SIK3 deletion and pterosin B treated mice using RNA sequencing (RNA-seq).
2024-07-21 | GSE234221 | GEO
Project description:Background: Paget's Disease of Bone (PDB) is characterized by excessive and disorganized bone remodeling, in which bone-resorbing osteoclasts play a key role. Strong genetic components and environmental factors contribute to the etiopathogenesis of PDB. We hypothesized that dysregulated microRNA (miR) expression contributed to the osteoclast phenotype in PDB. Results: From deep sequencing, six mature miRs, miR-29b1-3p, miR-15b-5p, miR-181a-5p, let7i-3p, miR-500b-5p, and miR-1246, were found to be significantly decreased in overactive osteoclasts from the PDB patients compared to those in the healthy controls. The differential expression of the miRs was confirmed by the analysis of a larger independent cohort using qPCR. Conclusion: We identified six miRNAs whose expression were deregulated in PDB condition. Many of these miRs are known to modulate many critical aspects of osteoclast generation and function by coordinating their regulation of gene expression. Our results enhance the understanding of osteoclast biology in PDB disease
2023-09-30 | GSE174180 | GEO
Project description:Genetic deletion of Nfatc1 in mice results in profound osteoclast-poor osteopetrosis, a high bone mass state caused by a lack of osteoclast activity. We hypothesized that the family of NFATc1 regulated transcripts in the osteoclast would be enriched for genes associated with osteoclast function. We used microarrays profile gene expression in wild-type and NFATc1-deficient osteoclasts generated in vitro to identify NFATc1-dependent transcripts in osteoclasts. Bone marrow macrophages from wild-type and mice with an induced deficiency of NFATc1 (NFATc1 fl/fl MxCre+ mice where NFATc1 excision was induced by polyIC treatment) were cultured ex vivo in MCSF and RANKL for 3 days. 2 biological replicates were assayed for each genotype.
2012-08-18 | E-GEOD-37219 | biostudies-arrayexpress
Project description:In osteolytic tumor, bone resportion can be occured after bone metastasis. Bone metastasis of colorectal cancer can induce obvious bone destruction. Aberrant activation of osteoclasts and the precursors is responsible for tumor-induced osteolysis. The biological process of osteoclast precursors could be modified by different tumor microenvironment. Microarrays were used to detail the differentially expressed genes or non-coding RNAs between normal osteoclast precursors and osteoclast precursors treated by secreta from CT-26 cells.
2021-08-14 | GSE182097 | GEO
Project description:Clinically, osteolytic phenotype is rare in prostate cancer. The molecular mechanism of bone metastasis in PCa is not fully understood. We performed RNA-seq to identify osteogenic and tumor associated roles in prostate cancer by a co-culture of osteoblasts (MG63) and prostate cancer cells (C4-2, C4-2B, 22Rv1 and DU145). We compared osteoblastic prostate cancer with osteolytic prostate cancer to evaluate the difference in phenotype of bone metastasis.
2023-09-26 | GSE210729 | GEO
Project description:Bisphosphonates are the mainstay of therapy worldwide for osteoporosis. They inhibit the activities of the osteoclasts, the bone resorption cells. While bisphosphonates are known to block farnesyl pyrophsophate synthase to exert their anti-resorptive action, the detailed mechanism is not well understood. Examining the change in expression profile before and after bisphosphonate treatment in the osteoclasts might shed some light on the biological pathways that are perturbed. Osteoclastic precursor cells were treated with (or without) bisphosphonates (alendronate or risedronate) during their differentiation into mature osteoclasts.
2014-11-06 | E-GEOD-63009 | biostudies-arrayexpress