C/EBPα and PU.1 exhibit different responses to RANK signaling for osteoclastogenesis

Jules, Joel; Li, Yiping; Chen, Wei

doi:10.1016/j.bone.2017.05.009

Cited by 9 publications

(10 citation statements)

References 61 publications

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“…As we just mentioned, these pathways were strongly associated with osteoblast differentiation and bone formation. There are also many studies demonstrated that up-regulated PU.1 may lead to osteoporosis by promoting osteoclast differentiation [ 36 – 39 ]. PU.1 may cause osteoclast differentiation and osteogenesis simultaneously in AS.…”

Section: Discussionmentioning

confidence: 99%

STAT3 and SPI1, may lead to the immune system dysregulation and heterotopic ossification in ankylosing spondylitis

Liang

Chen

et al. 2022

BMC Immunol

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Objective This study was aimed to identify the biomarkers for diagnosis and reveal the immune microenvironment changes in ankylosing spondylitis (AS). Methods GSE73754 was downloaded for the co-expression network construction and immune cell analyses. Flow cytometric analysis was performed to validate the results of bioinformatics analysis. Gene set enrichment analysis (GSEA) was performed to investigate the potential biological characteristic between different phenotypes. Pearson correlation analysis between the hub genes and the xCell score of immune cell types was performed. Results Signal transducer and activator of transcription 3 (STAT3) and Spi-1 proto-oncogene (SPI1) was identified as the hub genes in the datasets GSE73754. And the t-test showed that the expression level of STAT3 and SPI1 in the GSE73754 was significantly higher in AS and human leukocyte antigen (HLA)-B27(+) groups. Flow cytometric analysis showed that natural killer T cells (NKT) cells were upregulated, while Th1 cells were down-regulated in AS, which was consistent with the results obtained from bioinformatics analysis. STAT3 and SPI1 was correlated with the NKT cells and Th1 cells. Conclusion STAT3 and SPI1 may be a key cytokine receptor in disease progression in AS.

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Section: Discussionmentioning

confidence: 99%

STAT3 and SPI1, may lead to the immune system dysregulation and heterotopic ossification in ankylosing spondylitis

Liang

Chen

et al. 2022

BMC Immunol

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“…We isolated total RNA from cultured cells with TRIzol reagent (Life Technologies, Inc., Grand Island, NY, USA; 15596018). Total RNA was reversetranscribed to complementary DNA (cDNA) by SuperScript VILO Master Mix (Life Technologies, 11755050) [31]. We used SYBR Green reagents (Life Technologies, 4385610) and StepOne Real-Time PCR System (Life Technologies, Applied Biosystems) to perform quantitative reverse transcription PCR (qRT-PCR) [32].…”

Section: Quantitative Rt-pcr (Qrt-pcr) Analysismentioning

confidence: 99%

“…F-actin ring formation was evaluated as previously determined [31]. MBMs were cultured on bovine cortical bone slices in 24-well plates or directly cultured in wells of 96-well plates, then induced to osteoclasts by M-CSF and RANKL.…”

Section: Cell Immunofluorescent (If) Stain and F-actin Ring Stainmentioning

confidence: 99%

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F2r negatively regulates osteoclastogenesis through inhibiting the Akt and NFκB signaling pathways

Zhang¹,

Wang²,

Zhu³

et al. 2020

Int. J. Biol. Sci.

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G-protein-coupled receptors (GPCRs) are pivotal drug targets for many diseases. Coagulation Factor II Thrombin Receptor (F2R) is an important member of GPCR family that is highly expressed in osteoclasts. However, the role of F2r in osteoclasts is still unclear. Here, to examine the functions of F2r on osteoclast formation, differentiation, activation, survival, and acidification, we employed loss-of-function and gain-of-function approaches to study F2r using F2r-targeted short hairpin RNA (sh-F2r) lentivirus and overexpression plasmid pLX304-F2r lentivirus respectively, in mouse bone marrow cells (MBMs) induced osteoclasts. We used three shRNAs targeting F2r which had the ability to efficiently and consistently knock down the expression of F2r at different levels. Notably, F2r knockdown trigged a significant increase in osteoclast activity, number, and size, as well as promoted bone resorption and F-actin ring formation with increased osteoclast marker gene expression. Moreover, F2r overexpression blocked osteoclast formation, maturation, and acidification, indicating that F2r negatively regulates osteoclast formation and function. Furthermore, we investigated the mechanism(s) underlying the role of F2r in osteoclasts. We detected RANKL-induced signaling pathways related protein changes F2r knockdown cells and found significantly increased pAkt levels in sh-F2r infected cells, as well as significantly enhanced phosphorylation of p65 and IKBα in early stages of RANKL stimulation. These data demonstrated that F2r responds to RANKL stimulation to attenuate osteoclastogenesis through inhibiting the both F2r-Akt and F2r-NFκB signaling pathways, which lead a reduction in the expression of osteoclast genes. Our study suggests that targeting F2r may be a novel therapeutic approach for bone diseases, such as osteoporosis.

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“…Recently, C/EBPα was shown to be highly expressed in osteoclasts [36]. Overexpression studies revealed that PU.1 upregulates the expression of C/EBPα, while C/EBPα upregulates the expression of c-Fos and NFATc1 [36,37]. Forced expression studies revealed that C/EBPα can specify mouse bone marrow cells to become osteoclasts, suggesting that C/EBPα can induce osteoclast lineage priming and plays a role in regulating gene expression during the early stages of osteoclast differentiation [36].…”

Section: Transcriptional Regulators Of Osteoclast Gene Expressionmentioning

confidence: 99%

Regulation of Osteoclast Differentiation and Skeletal Maintenance by Histone Deacetylases

2019

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Bone is a dynamic tissue that must respond to developmental, repair, and remodeling cues in a rapid manner with changes in gene expression. Carefully-coordinated cycles of bone resorption and formation are essential for healthy skeletal growth and maintenance. Osteoclasts are large, multinucleated cells that are responsible for breaking down bone by secreting acids to dissolve the bone mineral and proteolytic enzymes that degrade the bone extracellular matrix. Increased osteoclast activity has a severe impact on skeletal health, and therefore, osteoclasts represent an important therapeutic target in skeletal diseases, such as osteoporosis. Progression from multipotent progenitors into specialized, terminally-differentiated cells involves carefully-regulated patterns of gene expression to control lineage specification and emergence of the cellular phenotype. This process requires coordinated action of transcription factors with co-activators and co-repressors to bring about proper activation and inhibition of gene expression. Histone deacetylases (HDACs) are an important group of transcriptional co-repressors best known for reducing gene expression via removal of acetyl modifications from histones at HDAC target genes. This review will cover the progress that has been made recently to understand the role of HDACs and their targets in regulating osteoclast differentiation and activity and, thus, serve as potential therapeutic target.

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C/EBPα and PU.1 exhibit different responses to RANK signaling for osteoclastogenesis

Cited by 9 publications

References 61 publications

STAT3 and SPI1, may lead to the immune system dysregulation and heterotopic ossification in ankylosing spondylitis

STAT3 and SPI1, may lead to the immune system dysregulation and heterotopic ossification in ankylosing spondylitis

F2r negatively regulates osteoclastogenesis through inhibiting the Akt and NFκB signaling pathways

Regulation of Osteoclast Differentiation and Skeletal Maintenance by Histone Deacetylases

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