Similar Datasets
Project description:We show that BRD9 suppresses osteoclastogenesis through negative feedback mechanism.
2023-02-20 | GSE222238 | GEO
Project description:We show that BRD9 suppresses osteoclastogenesis through negative feedback mechanism.
2023-02-20 | GSE222237 | GEO
Project description:We show that BRD9 suppresses osteoclastogenesis through negative feedback mechanism.
2023-02-20 | GSE222239 | GEO
Project description:Osteoclasts are bone-resorbing cells that undergo extensive changes in morphology throughout their differentiation. Altered osteoclast differentiation and activity lead to changes in pathological bone resorption. The mammalian target of rapamycin (mTOR) is a kinase, and aberrant mTOR complex 1 (mTORC1) signaling is associated with altered bone homeostasis. The activation of mTORC1 is biphasically regulated during osteoclastogenesis; however, the mechanism behind mTORC1-mediated regulation of osteoclastogenesis and bone resorption is incompletely understood. Here, we found that MYC coordinates the dynamic regulation of mTORC1 activation during osteoclastogenesis. MYC-deficiency blocked the early activation of mTORC1 and also reversed the decreased activity of mTORC1 at the late stage of osteoclastogenesis. The suppression of mTORC1 activity by rapamycin in mature osteoclasts enhances bone resorption activity despite the indispensable role of high mTORC1 activation in osteoclast formation in both mouse and human cells. Mechanistically, MYC induces Growth arrest and DNA damage-inducible protein (GADD34) expression and suppresses mTORC1 activity at the late phase of osteoclastogenesis. Taken together, our findings identify a MYC-GADD34 axis as an upstream regulator of dynamic mTORC1 activation in osteoclastogenesis and highlight the interplay between MYC and mTORC1 pathways in determining osteoclast activity.
2022-09-15 | GSE202932 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2023-02-20 | GSE222240 | GEO
Project description:Clarification of the mechanisms underlying osteoclast differentiation enable us to understand the physiology of bone metabolism as well as the pathophysiology of bone diseases, such as osteoporosis. Recently, it has been reported that epigenetics can determine the cell fate and regulate cell type specific gene expression. However, little is known about epigenetics during osteoclastogenesis. To reveal a part of epigenetics, especially focused on chromatin dynamics, during early osteoclastogenesis and identify novel transcription factors involved in osteoclastogenesis, we investigated genome-wide analysis of open chromatin during receptor activator of nuclear factor-M-NM-:B ligand (RANKL)-induced osteoclastogenesis using DNase I hypersensitive sites sequencing (DNase-seq). DNase-seq was performed using the extracted nuclei obtained from RAW264 cells treated with or without RANKL for 24 hours, followed by several bioinformatic analyses. DNase I hypersensitive sites (DHSs) during RANKL-induced osteoclastogenesis were dynamically changed and accumulated in promoter regions, although the distributions of DHSs among cis-regulatory DNA regions were identical regardless of RANKL stimulation. Motif discoveries from DHSs successfully identified well-known osteoclastogenic transcription factors such as Jun, CREB1, FOS, ATF2 and ATF4, but also novel transcription factors for osteoclastogenesis such as Zscan10, Atf1 Nrf1 and Srebf2. siRNA knockdown of these identified novel transcription factors impaired osteoclastogenesis. Taken together, DNase-seq can be a useful tool for comprehension of epigenetics, especially chromatin dynamics during osteoclastogenesis and for identification of novel transcription factors involved in osteoclastogenesis. This study may reveal underlying mechanisms that determine cell-type specific differentiation of bone cells and may lead to investigate novel therapeutic targets for osteoporosis. Examination of genome-wide DNase Hypersensitive Sites in differentiated and undifferentiated RAW264 cells.
2014-11-05 | E-GEOD-54139 | biostudies-arrayexpress
Project description:TNF plays a key role in inflammation and bone resorption. However, the mechanisms regulating TNF-mediated osteoclastogenesis remain largely unclear because its direct osteoclastogenic ability is weak. Here, we found that TGFβ priming enables TNF to effectively induce osteoclastogenesis from macrophages, independently of the osteoclastogenic action of RANKL. Lack of TGFβ signaling in macrophages suppresses inflammatory, but not physiological, osteoclastogenesis and bone resorption in vivo. Mechanistically, TGFβ priming reprograms macrophage response to TNF towards osteoclastogenesis by remodeling chromatin accessibility and histone modification. TGFβ and TNF induce an unconventional osteoclastogenic program, which includes the suppression of the TNF-induced IRF1-IFNβ-IFN stimulated gene (ISG) axis, promotion of IRF8 degradation and B-Myb induction. These mechanisms are present in RA, in which TGFβ level is elevated and correlated with osteoclast activity. Our findings identify a function and mechanism of action for TGFβ in TNF-mediated inflammatory osteoclastogenesis, and open avenues for selective treatment of inflammatory bone loss.
2022-03-24 | GSE171839 | GEO
Project description:TNF plays a key role in inflammation and bone resorption. However, the mechanisms regulating TNF-mediated osteoclastogenesis remain largely unclear because its direct osteoclastogenic ability is weak. Here, we found that TGFβ priming enables TNF to effectively induce osteoclastogenesis from macrophages, independently of the osteoclastogenic action of RANKL. Lack of TGFβ signaling in macrophages suppresses inflammatory, but not physiological, osteoclastogenesis and bone resorption in vivo. Mechanistically, TGFβ priming reprograms macrophage response to TNF towards osteoclastogenesis by remodeling chromatin accessibility and histone modification. TGFβ and TNF induce an unconventional osteoclastogenic program, which includes the suppression of the TNF-induced IRF1-IFNβ-IFN stimulated gene (ISG) axis, promotion of IRF8 degradation and B-Myb induction. These mechanisms are present in RA, in which TGFβ level is elevated and correlated with osteoclast activity. Our findings identify a function and mechanism of action for TGFβ in TNF-mediated inflammatory osteoclastogenesis, and open avenues for selective treatment of inflammatory bone loss.
2022-03-24 | GSE171841 | GEO
Project description:TNF plays a key role in inflammation and bone resorption. However, the mechanisms regulating TNF-mediated osteoclastogenesis remain largely unclear because its direct osteoclastogenic ability is weak. Here, we found that TGFβ priming enables TNF to effectively induce osteoclastogenesis from macrophages, independently of the osteoclastogenic action of RANKL. Lack of TGFβ signaling in macrophages suppresses inflammatory, but not physiological, osteoclastogenesis and bone resorption in vivo. Mechanistically, TGFβ priming reprograms macrophage response to TNF towards osteoclastogenesis by remodeling chromatin accessibility and histone modification. TGFβ and TNF induce an unconventional osteoclastogenic program, which includes the suppression of the TNF-induced IRF1-IFNβ-IFN stimulated gene (ISG) axis, promotion of IRF8 degradation and B-Myb induction. These mechanisms are present in RA, in which TGFβ level is elevated and correlated with osteoclast activity. Our findings identify a function and mechanism of action for TGFβ in TNF-mediated inflammatory osteoclastogenesis, and open avenues for selective treatment of inflammatory bone loss.
2022-03-24 | GSE171842 | GEO
Project description:Osteoclasts are multinucleated cells specialized in degrading the mineralized bone matrix. Osteoclast differentiation and function are tightly regulated, to prevent excessive or insufficient bone resorption. Several control mechanisms participate in modulating osteoclastogenesis, and an increasing number of reports describe the role of microRNAs (miRNAs) in this process. Disrupting the expression of specific miRNAs can result in alterations of osteoclast formation and bone homeostasis. We and others have previously characterized 9 miRNAs whose levels change during osteoclast differentiation, and identified some of the target genes that mediate their function. However, little is known about changes in the miRNA expression profile during osteoclastogenesis. In this study, we isolated a murine primary bone marrow population enriched for osteoclast precursors, and used the Agilent microarray platform to analyze the expression of mature miRNAs after 1, 3, and 5 days of RANKL-driven differentiation. 93 miRNAs showed greater than 2 fold-change during these early, middle, and late stages of osteoclastogenesis. Many of these miRNAs were detected for the first time in osteoclasts, and we validated the expression of selected miRNAs by quantitative RT-PCR. We identified clusters of differentially expressed miRNAs, and performed computational analyses to predict functional pathways that may be regulated by these miRNAs. Several miRNAs were predicted to regulate genes involved in cytoskeletal remodeling, a crucial mechanism for the migration of osteoclast precursors, their maturation, and bone resorbing activity. Our results suggest that clusters of miRNAs differentially expressed during the course of osteoclastogenesis converge on the regulation of several key functional pathways. Overall, this study identified miRNAs expressed during early, middle and late osteoclastogenesis, contributing to understanding the molecular mechanisms regulating this complex differentiation process. Mouse primary bone marrow cultures were enriched for osteoclast precursors by depletion of B220/CD45R+ and CD3+ cells (B and T lymphocytes, respectively). Cells were differentiated with M-CSF and RANKL, and miRNA expression was analyzed at days 1, 3, and 5. Four biological replicates for each time point were used.
2015-12-31 | E-GEOD-53017 | biostudies-arrayexpress