Effect of vitamin D and K on osteoclast differentiation of bone marrow derived macrophages induced by RANKL
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE272401 | GEO | 2025/06/16
REPOSITORIES: GEO
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Project description:To investigate effect of RANKL on osteoclast differentiation, bone marrow cells were cultured with M-CSF and RANKL.
2023-11-08 | GSE225883 | GEO
Project description:Purpose: Among the diverse cytokines involved in osteoclast differentiation, IL-3 has been shown to inhibit RANKL-induced osteoclastogenesis. However, the mechanism underlying IL-3-mediated inhibition of osteoclast differentiation is not fully understood. In the present study, we demonstrate that IL-3 activation of STAT5 inhibits RANKL-induced osteoclastogenesis through the induction of Id genes. Methods: To investigate the effect of STAT5 on osteoclast differentiation and IL-3-mediated inhibition of osteoclast differentiation, bone marrow derived macrophages isolated from STAT5 wild-type (Stat5fl/fl) or STAT5 cKO (STAT5;MX1-Cre) were differentiated to osteoclast in the presence of M-CSF and RANKL with or without IL-3; and bone marrow derived macrophges from STAT5 wild-type and STAT5 cKO were overexpressed with PMX-FIG (control) or STAT5A1*6 (constitutively active form of STAT5A) and differentiated to osteoclast. To analyze bone phenotype, femurs and tibiae of 16 week-old STAT5 wild-type and STAT5 cKO were subjected to micro CT analysis and histomorphometry, respectively. Results: Overexpression of STAT5 inhibited RANKL-induced osteoclastogenesis. However, RANKL did not regulate either expression or activation of STAT5 during osteoclast differentiation. STAT5 deficiency prevented IL-3-mediated inhibition of osteoclastogenesis, suggesting that STAT5 plays an important role in IL-3-mediated inhibition of osteoclast differentiation. In addition, IL-3-induced STAT5 activation upregulated expression of the Id1 and Id2 genes, which are negative regulators of osteoclastogenesis. Overexpression of ID1 or ID2 in STAT5-deficient cells reversed osteoclast development recovered from IL-3-mediated inhibition. Moreover, micro-computed tomography and histomorphometric analysis revealed that STAT5 conditional knockout mice showed reduced bone mass, with an increased number of osteoclasts. Furthermore, IL-3 inhibited RANKL-induced osteoclast differentiation less effectively in STAT5 conditional knockout mice than in wild-type mice in a RANKL injection model. Conclusion: Taken together, our results suggest that STAT5 is a key transcription factor for IL-3-mediated inhibition of RANKL-induced osteoclastogenesis through Id gene expression. Examination of 4 different combination of osteoclast differentiation condition of bone marrow derived macrophages.
2016-08-03 | E-GEOD-76988 | biostudies-arrayexpress
Project description:To identify the microRNAs that are involved in osteoclastogenesis, microRNA expression profiles in mouse bone marrow macrophages (BMMs) stimulated with RANKL (BMOc) were compared with that of control untreated BMMs. These results provide insights into the mechanisms to regulate osteoclastogenesis and bone resorption activities in osteoclasts by microRNA. BMMs were cultured with 20 ng/ml M-CSF in the presence or absence of 50 ng/ml RANKL for 24 hours. Cells were collected for total RNA isolation, and were subjected to microRNA array analysis.
2013-07-10 | E-GEOD-48629 | biostudies-arrayexpress
Project description:Peroxiredoxin 1 (PRDX1), traditionally known as an intracellular antioxidant enzyme, has emerged as a regulator of inflammatory responses via Toll-like receptor 4 (TLR4) signaling. Despite this, the mechanistic details of the PRDX1-TLR4 axis and its impact on osteoclast differentiation remain elusive. Here, we show that PRDX1 suppresses RANKL-induced osteoclast differentiation. Utilizing pharmacological inhibitors, we reveal that PRDX1 inhibits osteoclastogenesis through both TLR4/TRIF and TLR4/MyD88 pathways. Transcriptome analysis revealed PRDX1-mediated alterations in gene expression, particularly upregulating serum amyloid A3 (SAA3) and aconitate decarboxylase 1 (ACOD1), known inhibitors of osteoclast differentiation. Mechanistically, PRDX1-TLR4 signaling activates p65, promoting SAA3 and ACOD1 expression while inhibiting NFATc1, a master regulator of osteoclastogenesis. Remarkably, PRDX1 redirects p65 binding from NFATc1 to SAA3/ACOD1 promoters, thereby suppressing osteoclast formation. Structural analysis showed that monomeric variants of PRDX1 with enhanced TLR4 binding exhibit potent inhibition of osteoclast differentiation. Our findings elucidate the inhibitory role of PRDX1-TLR4 axis in osteoclastogenesis, providing insights into therapeutic strategies for bone-related disorders.
2024-11-12 | GSE267039 | GEO
Project description:To identify the microRNAs that are involved in osteoclastogenesis, microRNA expression profiles in mouse bone marrow macrophages (BMMs) stimulated with RANKL (BMOc) were compared with that of control untreated BMMs. These results provide insights into the mechanisms to regulate osteoclastogenesis and bone resorption activities in osteoclasts by microRNA.
2013-07-10 | GSE48629 | GEO
Project description:Purpose: Among the diverse cytokines involved in osteoclast differentiation, IL-3 has been shown to inhibit RANKL-induced osteoclastogenesis. However, the mechanism underlying IL-3-mediated inhibition of osteoclast differentiation is not fully understood. In the present study, we demonstrate that IL-3 activation of STAT5 inhibits RANKL-induced osteoclastogenesis through the induction of Id genes. Methods: To investigate the effect of STAT5 on osteoclast differentiation and IL-3-mediated inhibition of osteoclast differentiation, bone marrow derived macrophages isolated from STAT5 wild-type (Stat5fl/fl) or STAT5 cKO (STAT5;MX1-Cre) were differentiated to osteoclast in the presence of M-CSF and RANKL with or without IL-3; and bone marrow derived macrophges from STAT5 wild-type and STAT5 cKO were overexpressed with PMX-FIG (control) or STAT5A1*6 (constitutively active form of STAT5A) and differentiated to osteoclast. To analyze bone phenotype, femurs and tibiae of 16 week-old STAT5 wild-type and STAT5 cKO were subjected to micro CT analysis and histomorphometry, respectively. Results: Overexpression of STAT5 inhibited RANKL-induced osteoclastogenesis. However, RANKL did not regulate either expression or activation of STAT5 during osteoclast differentiation. STAT5 deficiency prevented IL-3-mediated inhibition of osteoclastogenesis, suggesting that STAT5 plays an important role in IL-3-mediated inhibition of osteoclast differentiation. In addition, IL-3-induced STAT5 activation upregulated expression of the Id1 and Id2 genes, which are negative regulators of osteoclastogenesis. Overexpression of ID1 or ID2 in STAT5-deficient cells reversed osteoclast development recovered from IL-3-mediated inhibition. Moreover, micro-computed tomography and histomorphometric analysis revealed that STAT5 conditional knockout mice showed reduced bone mass, with an increased number of osteoclasts. Furthermore, IL-3 inhibited RANKL-induced osteoclast differentiation less effectively in STAT5 conditional knockout mice than in wild-type mice in a RANKL injection model. Conclusion: Taken together, our results suggest that STAT5 is a key transcription factor for IL-3-mediated inhibition of RANKL-induced osteoclastogenesis through Id gene expression.
2016-08-03 | GSE76988 | GEO
Project description:GDF11 treatment leads to bone loss in mice and strongly stimulates RANKL-induced osteoclastogenesis of bone marrow-derived macrophages (BMMs) in vitro. We used microarrays to identified distinct classes of up-regulated genes in BMMs after GDF11 treatment. Mouse BMMs were treated with or without GDF11 for RNA extraction and and hybridization on Affymetrix microarrays
2016-07-21 | E-GEOD-84609 | biostudies-arrayexpress
Project description:GDF11 treatment leads to bone loss in mice and strongly stimulates RANKL-induced osteoclastogenesis of bone marrow–derived macrophages (BMMs) in vitro. We used microarrays to identified distinct classes of up-regulated genes in BMMs after GDF11 treatment.
2016-07-21 | GSE84609 | GEO
Project description:Bone remodeling, crucial for skeletal integrity, involves osteoclasts and osteoblasts. Osteoclastogenesis, regulated by NFATc1, is activated by c-Fos and NF-κB signaling in response to RANKL. Excessive RANKL signaling contributes to bone loss pathology. Here we reveal denatonium as an inhibitor of RANKL-induced osteoclast differentiation through the p65 pathway. RNA-seq identified downregulated osteoclast-related genes. Affinity chromatography pinpointed 35 denatonium-interacting proteins, with PRDX1 showing specificity. PRDX1 deficiency led to osteoporosis with increased osteoclast activity and enhanced RANKL-induced osteoclast formation. Denatonium blocked PRDX1 lysosomal degradation, stabilizing PRDX1. Through transcription factor binding site analysis, p65 emerged as a major target suppressed by the denatonium-PRDX1 interaction. Chromatin immunoprecipitation confirmed that the denatonium-PRDX1 complex inhibited p65 enrichment at promoter regions critical for osteoclast differentiation. In an osteoporosis animal model, denatonium treatment restored bone health. This study uncovers denatonium's novel role in bone formation regulation by selectively targeting PRDX1, suggesting its potential in osteoporosis treatment.
2024-06-30 | GSE248992 | GEO
Project description:Bone remodeling, crucial for skeletal integrity, involves osteoclasts and osteoblasts. Osteoclastogenesis, regulated by NFATc1, is activated by c-Fos and NF-κB signaling in response to RANKL. Excessive RANKL signaling contributes to bone loss pathology. Here we reveal denatonium as an inhibitor of RANKL-induced osteoclast differentiation through the p65 pathway. RNA-seq identified downregulated osteoclast-related genes. Affinity chromatography pinpointed 35 denatonium-interacting proteins, with PRDX1 showing specificity. PRDX1 deficiency led to osteoporosis with increased osteoclast activity and enhanced RANKL-induced osteoclast formation. Denatonium blocked PRDX1 lysosomal degradation, stabilizing PRDX1. Through transcription factor binding site analysis, p65 emerged as a major target suppressed by the denatonium-PRDX1 interaction. Chromatin immunoprecipitation confirmed that the denatonium-PRDX1 complex inhibited p65 enrichment at promoter regions critical for osteoclast differentiation. In an osteoporosis animal model, denatonium treatment restored bone health. This study uncovers denatonium's novel role in bone formation regulation by selectively targeting PRDX1, suggesting its potential in osteoporosis treatment.
2024-06-30 | GSE248993 | GEO