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PKM2 regulates osteoclastogenesis by affecting osteoclast precursor cell fusion via down-regulation of OC-STAMP and DC-STAMP

ABSTRACT: PKM2 regulates osteoclastogenesis by affecting osteoclast precursor cell fusion via down-regulation of OC-STAMP and DC-STAMP

PROVIDER: PRJNA780897 | ENA |

REPOSITORIES: ENA

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PKM2 regulates osteoclastogenesis by affecting osteoclast precursor cell fusion via down-regulation of OC-STAMP and DC-STAMP

Project description:Osteoporosis is a common bone disease that has become a serious public health problem with the aging of population. Osteoclasts are the only cells in body that can resorb bone, whose dysfunction is closely related to osteoporosis. Pyruvate kinase M2 (PKM2) is one of the essential rate-limiting enzymes in the process of glycolysis. This study aimed to elucidate the role of PKM2 in osteoclastogenesis and bone resorption. Bone marrow-derived macrophages (BMMs) were transfected with adenovirus to knock down the expression of PKM2 gene or treated with the PKM2 activators TEPP-46 and DASA-58. Osteoclast formation was detected by TRAP staining, osteoclast-specific gene and protein expression was detected by RT-qPCR and Western blotting, and the effect of DASA-58 on osteoclast gene expression at the transcriptional level was examined by RNA-seq. The results showed that knockdown of PKM2 by adenoviral transfection or treatment with PKM2 activators TEPP-46 and DASA-58 inhibited osteoclast differentiation and suppressed the expression of osteoclast-associated genes in BMMs. Furthermore, PKM2 activators TEPP-46 and DASA-58 could inhibit several signaling pathways in osteoclasts; knockdown of PKM2 or treatment with PKM2 activators TEPP-46 and DASA-58 both affected osteoclast precursor cell fusion by inhibiting the expression of osteoclast stimulatory transmembrane protein (OC-STAMP) and dendritic cell-specific transmembrane protein (DC-STAMP). Therefore, PKM2 is closely related to osteoclast differentiation and formation, and the development of new therapeutic strategies targeting the PKM2 gene in osteoclasts may be feasible for the prevention and treatment of osteoporosis.

2025-03-17 | GSE188963 | GEO

Chromatin accessibility-based epigenetic landscape in osteoclastogenesis [ATAC-seq]

Project description:In this study, we showed chromatin accessibility-based epigenetic landscape in osteoclastogenesis. To reveal chromatin accessibility landscape throughout osteoclastogenesis, we conducted Assay for Transposase Accessible Chromatin with high-throughput sequencing (ATAC-seq) with BMM (D0), OC precursors day 1 (D1), OC precursor day 2 (D2), and OC (D3).

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Osteoclast stimulatory transmembrane protein (OC-STAMP), a novel protein induced by RANKL that promotes osteoclast differentiation.

Project description: Not available

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Chromatin accessibility-based epigenetic landscape in osteoclastogenesis [RNA-seq]

Project description:In this study, we showed chromatin accessibility-based epigenetic landscape in osteoclastogenesis. To reveal the affected genes by alteration in histone acetylation states after RANKL stimulation, we supplemented sodium acetate, which increased histone acetylation, to OC precursors. Then we conducted RNA-seq with BMM (D0), OC precursors (D1), and OC precursors treaed with sodium acetate (ACD1).

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M-CSF priming of osteoclast precursors can cause osteoclastogenesis-insensitivity, which can be prevented and overcome on bone

Project description:Comparison of gene expression of the osteoclast precursor myeloid blast seeded on plastic and on bone, primed with M-CSF for 4 days and culture with M-CSF and RANKL for 1 day. Osteoclasts and macrophages share progenitors that must receive decisive lineage signals driving them into their respective differentiation routes. Macrophage colony stimulation factor M-CSF is a common factor; bone is likely the stimulus for osteoclast differentiation. To elucidate the effect of both, shared mouse bone marrow precursor myeloid blast was pre-cultured with M-CSF on plastic and on bone. M-CSF priming prior to stimulation with M-CSF and osteoclast differentiation factor RANKL resulted in a complete loss of osteoclastogenic potential without bone. This coincided with a steeply decreased expression of osteoclast genes TRACP and DC-STAMP, but an increased expression of the macrophage markers F4/80 and CD11b. Compellingly, M-CSF priming on bone accelerated the osteoclastogenic potential: M-CSF primed cells that had received only one day M-CSF and RANKL and were grown on bone already expressed an array of genes that are associated with osteoclast differentiation and these cells differentiated into osteoclasts within 2 days. This implies that adhesion to bone dictates the fate of osteoclast precursors. Common macrophage-osteoclast precursors may become insensitive to differentiate into osteoclasts and regain osteoclastogenesis when bound to bone or when in the vicinity of bone. Two conditions: Osteoclast precursors on plastic and on bone, n=4, dye swap

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Germline loss of PKM2 promotes metabolic distress and hepatocellular carcinoma

Project description:Alternative splicing of the Pkm gene product generates the PKM1 and PKM2 isoforms of pyruvate kinase, and PKM2 expression is closely linked to embryogenesis, tissue regeneration, and cancer. To interrogate the functional requirement for PKM2 during development and tissue homeostasis, we generated germline PKM2 null mice (Pkm2-/-). Unexpectedly, despite being the primary isoform expressed in most wild-type adult tissues, we found that Pkm2-/- mice are viable and fertile. Thus, PKM2 is not required for embryonic or postnatal development. Loss of PKM2 leads to compensatory expression of PKM1 in the tissues that normally express PKM2. Strikingly, PKM2 loss leads to spontaneous development of hepatocellular carcinoma (HCC) with high penetrance that is accompanied by progressive changes in systemic metabolism characterized by altered systemic glucose homeostasis, inflammation, and hepatic steatosis. Therefore, in addition to its role in cancer metabolism, PKM2 plays a role in controlling systemic metabolic homeostasis and inflammation, thereby preventing HCC by a non-cell-autonomous mechanism. RNA was isolated from flash frozen ground whole liver tissue of 35 week old PKM2 KO and WT mice. Three independent mice from each condition were used as biological replicates.

2016-03-25 | E-GEOD-79535 | biostudies-arrayexpress

Identification of differentially expressed genes and molecular pathways involved in osteoclastogenesis using RNA-seq

Project description:In order to explore genes involved in osteoclastogenesis, we performed a differential gene expression analysis comparing human osteoclast (OC)-like cells with their precursor peripheral blood mononuclear cells (PBMC).

2023-04-14 | GSE225974 | GEO

Transcriptional profiles of genes in the early stage of osteoclastogenesis

Project description:Osteoclast (OC) differentiation undergoes a two-step process: commitment of hematopoietic progenitor cells to tartrate-resistant acid phosphatase (TRAcP) positive OC precursors (OCPs), and fusion of OCPs into multinucleated OCs. In order to identify transcriptional profiles of genes in the transitional phase between OC commitment and fusion in OCG, Affymetrix® Mouse Gene 1.0 ST arrays were performed on total RNA extracted from mouse (SV129/BL6 ) monocytes and pre-osteoclasts (pre-OCs), primed with macrophage colony-stimulated factor (M-CSF) or M-CSF and soluble recombinant receptor activator of NF-кB ligand (sRANKL), respectively. The analysis identified 656 RANKL-up or down-regulated in the early stage of osteoclastogenesis.

2014-02-17 | GSE54779 | GEO

Transcriptional profiles of genes in the early stage of osteoclastogenesis

Project description:Osteoclast (OC) differentiation undergoes a two-step process: commitment of hematopoietic progenitor cells to tartrate-resistant acid phosphatase (TRAcP) positive OC precursors (OCPs), and fusion of OCPs into multinucleated OCs. In order to identify transcriptional profiles of genes in the transitional phase between OC commitment and fusion in OCG, AffymetrixM-BM-. Mouse Gene 1.0 ST arrays were performed on total RNA extracted from mouse (SV129/BL6 ) monocytes and pre-osteoclasts (pre-OCs), primed with macrophage colony-stimulated factor (M-CSF) or M-CSF and soluble recombinant receptor activator of NF-M-PM-:B ligand (sRANKL), respectively. The analysis identified 656 RANKL-up or down-regulated in the early stage of osteoclastogenesis. Monocytes isolated from mouse bone marrow were stimulated with M-CSF and soluble RANKL (m + r), or M-CSF alone (m).

2014-02-17 | E-GEOD-54779 | biostudies-arrayexpress

OC-STAMP promotes osteoclast fusion for pathogenic bone resorption in periodontitis via up-regulation of permissive fusogen CD9.

Project description: Not available

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