Macrophages and osteoclasts stem from a bipotent progenitor that lies downstream of the common macrophage/osteoclast/dendritic cell progenitor
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE97380 | GEO | 2018/02/13
REPOSITORIES: GEO
Similar Datasets
Project description:Monocytes/macrophages (MΦs), osteoclasts (OCs), and dendritic cells (DCs) are closely related cell types of high clinical significance, but the exact steps in their lineage commitment are unclear. In studies on MΦ and DC development, OC development is generally not addressed. Furthermore, findings on DC development are confusing, because monocytes can also differentiate into DC-like cells. To resolve these issues, we have examined the development of monocytes/MΦs, OCs, and DCs from common progenitors, using the homeostatic driver cytokines macrophage colony-stimulating factor, RANK ligand (L), and Flt3L. In mouse bone marrow, B220-CD11blow/-c-Kit+c-Fms+ cells could be dissected into a CD27+Flt3+ population that proved oligopotent for MΦ/OC/DC development (MODP) and a CD27low/-Flt3- population that proved bipotent for MΦ/OC development (MOP). Developmental potential and relationship of MODP and downstream MOP populations are demonstrated by differentiation cultures, functional analysis of MΦ/OC/DC offspring, and genome-wide messenger RNA expression analysis. A common DC progenitor (CDP) has been described as committed to plasmacytoid and conventional DC development. However, the human CDP proved identical to the MODP population, whereas the mouse CDP largely overlapped with the MODP population and was accordingly oligopotent for MΦ, OC, and DC development. The CX3CR1+ MΦ/DC progenitor (MDP) population described in the mouse generated MΦs and OCs but not DCs. Thus, monocytes/MΦs, OCs, and DCs share a common progenitor that gives rise to a bipotent MΦ/OC progenitor, but a dedicated DC progenitor is currently undefined. The definition of these progenitor populations may serve diagnostics and interventions in diseases with pathogenic activity of MΦs, OCs, or DCs.
| S-EPMC5728283 | biostudies-literature
Project description:Osteoclasts are derived from the monocyte/macrophage lineage, but little is known about osteoclast precursors in circulation. Bone marrow cells were subdivided into three populations; RANKhighFmslow, RANKhighFmshigh and RANKlowFmshigh. GeneChip analysis confirmed that the expression levels of monocyte-macrophage markers such as Emr1 (F4/80), Itgam (CD11b) and Csf1 (c-Fms) were lower in the RANKhighFmslow than RANKlowFmshigh population. In contrast, cells in the RANKhighFmslow population expressed higher levels of osteoclast markers such as Car ll (carbonic anhydrase ll), Mmp9 (matrix metalloproteinase 9), Acp5 (acid phosphatase 5) and Tfrc (transferrin receptor). These results suggest that RANKhighFmslow cells express few of the phenotypes of monocytes, and their differentiation into osteoclasts occurs at a slightly more advanced stage than that of the RANKlowFmshigh population. RANKhighFmslow cells and RANKlowFmshigh cells were isolated from bone marrow in ddY mice by FACS (Fluorescent activated cell sorting). Differential expression levels of mRNA were determined by GeneChip analysis.
2012-01-07 | E-GEOD-26499 | biostudies-arrayexpress
Project description:To understand how interactions of myeloma cells with osteoclasts and mesenchymal stem cells in the bone marrow affect the clinical course of myeloma, we used microarrays to study changes in gene expression in freshly isolated myeloma plasma cells following co-cultures with osteoclasts (8 experiments) or with mesenchymal stem cells (13 experiments). Interaction with osteoclasts induced changes in the expression of 675 genes, and interaction with mesenchymal stem cells induced changes in the expression of 296 genes. Expression of only 58 genes commonly and similarly changed in both co-culture systems. Among these, we identified genes associated with overall, progression-free, and post-relapse survival, and developed survival prediction models. Gene expression data from 347 patients treated with total therapy 2 protocol, 433 with total therapy 3, and 98 patients who received various treatments (91 of them high-dose therapy with autologous stem cell support) were used for the analysis. Good predictive models were developed only for post-relapse survival, using genes involved in interaction with osteoclasts or with mesenchymal stem cells. The best predictive model used expression of first relapse of 33 probesets whose expression changed in myeloma cells following interaction with osteoclasts, with hazard ratios of 24, 20, and 12 for patients who relapsed following total therapy 2, total therapy 3 and the various other treatments, respectively. Among the probesets used for prediction, only 10, representing 8 genes, were commonly changed after both co-culture systems. These could present favorable target for therapy. Global gene expression profiling of osteoclasts (OCs) before and after co-culture with primary multiple myeloma plasma cells (MMPCs) was done using Affymetrix microarrays. Eight MMPC and OC co-culture experiments were performed using MMPC isolated from 8 patients and OC prepared from 8 different patients.
2015-08-13 | E-GEOD-31156 | biostudies-arrayexpress
Project description:Osteoclasts are multinucleated, bone-resorbing cells. However, they also digest cartilage during skeletal maintenance, development and in degradative conditions including osteoarthritis, rheumatoid arthritis and primary bone sarcoma. This study explores the mechanisms behind the osteoclast–cartilage interaction. Human osteoclasts differentiated on acellular human cartilage expressed osteoclast marker genes (e.g. CTSK, MMP9) and proteins (TRAP, VNR), visibly damaged the cartilage surface and released glycosaminoglycan in a contact-dependent manner. Direct co-culture with chondrocytes during differentiation increased large osteoclast formation (p < 0.0001) except when co-cultured on dentine, when osteoclast formation was inhibited (p = 0.0002). Osteoclasts cultured on dentine inhibited basal cartilage degradation (p = 0.012). RNA-seq identified MMP8 overexpression in osteoclasts differentiated on cartilage versus dentine (8.89-fold, p = 0.0133), while MMP9 was the most highly expressed MMP. Both MMP8 and MMP9 were produced by osteoclasts in osteosarcoma tissue. This study suggests that bone-resident osteoclasts and chondrocytes exert mutually protective effects on their ‘native’ tissue. However, when osteoclasts contact non-native cartilage they cause degradation via MMPs. Understanding the role of osteoclasts in cartilage maintenance and degradation might identify new therapeutic approaches for pathologies characterized by cartilage degeneration.
2021-12-01 | GSE166535 | GEO
Project description:Osteoclasts are derived from the monocyte/macrophage lineage, but little is known about osteoclast precursors in circulation. Bone marrow cells were subdivided into three populations; RANKhighFmslow, RANKhighFmshigh and RANKlowFmshigh. GeneChip analysis confirmed that the expression levels of monocyte-macrophage markers such as Emr1 (F4/80), Itgam (CD11b) and Csf1 (c-Fms) were lower in the RANKhighFmslow than RANKlowFmshigh population. In contrast, cells in the RANKhighFmslow population expressed higher levels of osteoclast markers such as Car ll (carbonic anhydrase ll), Mmp9 (matrix metalloproteinase 9), Acp5 (acid phosphatase 5) and Tfrc (transferrin receptor). These results suggest that RANKhighFmslow cells express few of the phenotypes of monocytes, and their differentiation into osteoclasts occurs at a slightly more advanced stage than that of the RANKlowFmshigh population.
2012-01-07 | GSE26499 | GEO
Project description:To understand how interactions of myeloma cells with osteoclasts and mesenchymal stem cells in the bone marrow affect the clinical course of myeloma, we used microarrays to study changes in gene expression in freshly isolated myeloma plasma cells following co-cultures with osteoclasts (8 experiments) or with mesenchymal stem cells (13 experiments). Interaction with osteoclasts induced changes in the expression of 675 genes, and interaction with mesenchymal stem cells induced changes in the expression of 296 genes. Expression of only 58 genes commonly and similarly changed in both co-culture systems. Among these, we identified genes associated with overall, progression-free, and post-relapse survival, and developed survival prediction models. Gene expression data from 347 patients treated with total therapy 2 protocol, 433 with total therapy 3, and 98 patients who received various treatments (91 of them high-dose therapy with autologous stem cell support) were used for the analysis. Good predictive models were developed only for post-relapse survival, using genes involved in interaction with osteoclasts or with mesenchymal stem cells. The best predictive model used expression of first relapse of 33 probesets whose expression changed in myeloma cells following interaction with osteoclasts, with hazard ratios of 24, 20, and 12 for patients who relapsed following total therapy 2, total therapy 3 and the various other treatments, respectively. Among the probesets used for prediction, only 10, representing 8 genes, were commonly changed after both co-culture systems. These could present favorable target for therapy. Global gene expression profiling of primary multiple myeloma plasma cells (MMPCs) before and after interaction with osteoclasts (OCs) was done using Affymetrix microarrays.
2019-08-21 | GSE31154 | GEO
Project description:To understand how interactions of myeloma cells with osteoclasts and mesenchymal stem cells in the bone marrow affect the clinical course of myeloma, we used microarrays to study changes in gene expression in freshly isolated myeloma plasma cells following co-cultures with osteoclasts (8 experiments) or with mesenchymal stem cells (13 experiments). Interaction with osteoclasts induced changes in the expression of 675 genes, and interaction with mesenchymal stem cells induced changes in the expression of 296 genes. Expression of only 58 genes commonly and similarly changed in both co-culture systems. Among these, we identified genes associated with overall, progression-free, and post-relapse survival, and developed survival prediction models. Gene expression data from 347 patients treated with total therapy 2 protocol, 433 with total therapy 3, and 98 patients who received various treatments (91 of them high-dose therapy with autologous stem cell support) were used for the analysis. Good predictive models were developed only for post-relapse survival, using genes involved in interaction with osteoclasts or with mesenchymal stem cells. The best predictive model used expression of first relapse of 33 probesets whose expression changed in myeloma cells following interaction with osteoclasts, with hazard ratios of 24, 20, and 12 for patients who relapsed following total therapy 2, total therapy 3 and the various other treatments, respectively. Among the probesets used for prediction, only 10, representing 8 genes, were commonly changed after both co-culture systems. These could present favorable target for therapy. Global gene expression profiling of osteoclasts (OCs) before and after co-culture with primary multiple myeloma plasma cells (MMPCs) was done using Affymetrix microarrays.
2015-08-13 | GSE31156 | GEO
Project description:Purpose: DCIR is an inhibitory type of C-type lectin receptor that regulates osteoclast (OC) formation and functions. This study aimed to find the genes of OCs that could be regulated through DCIR. Method: Bone marrow cells from WT and Dcir-/- mice were cultured in M-CSF for 2 days and the the cells were further cultured in M-CSF and RANKL. RNA profiles were generated by deep sequencing, in triplicate, using Illumina NovaSeq. Results: We detected xxx gense that were higher expression in Dcir-/- OCs, compared with WT OCs, with a fold change ≥1.5 and p value <0.05. Conclusion: Our data showed that Dcir deficiency in OCs changed the gene expression pattern, compared to WT OCs, which are induced by M-CSF and RANKL.
2023-06-07 | GSE223429 | GEO
Project description:Transcriptional profiling of mouse osteoclasts comparing control osteoclasts from Stat5 flox mice with osteoclasts from Stat5 cKO mice. Two-condition experiment, Stat5 flox cells vs. Stat5 cKO cells
2013-12-09 | E-GEOD-51283 | biostudies-arrayexpress
Project description:Balanced osteoclast differentiation is crucial in maintaining skeleton health through life. Receptor activator of nuclear factor kappa-Β (RANK) is indispensable for OCs normal development in vivo and for the in vitro fusion of circulating progenitor cells into OCs. Many cytokines enhance RANK and RANK-ligand (RANK-L)-mediated differentiation of myeloid cells into OCs. In particular, tumor necrosis factor (TNF) is recognized as a potent activator and is associated with in vivo bone destruction in the context of OC dysregulation in inflammatory arthritis. Paradoxically, infiltration of monocytes into TNF rich inflammatory sites does not lead to a preponderance of osteoclasts but rather macrophages. Recent in vivo murine studies have shown how circulating myeloid precursors play a crucial role in post-natal OC differentiation and skeletal health. However, little is known about such pathways in humans. Herein we demonstrate that, unexpectedly TNF can act as a critical homeostatic regulator of human CD14+ monocyte differentiation into osteoclast by inhibiting osteoclastogenesis to favour macrophage development. In contrast, a distinct, previously unidentified human CD11c+ myeloid pre-osteoclast population is exempt from this negative regulation. In healthy humans, to control cell fate and specifically overcome OC differentiation, TNF drives epigenetic modification of the RANK promoter via a TNFR1-IKK-dependent pathway. In contrast in rheumatoid arthritis, patient-derived monocytes exhibit an altered epigenetic state that results in dysregulated TNF-mediated osteoclast homeostasis providing a pathologic consequence of failure of this pathway.
2021-03-25 | GSE152912 | GEO