Similar Datasets
Project description:As a part of the skeletal system, bone marrow environment also performs vital functions in maintaining the bone homeostasis. To gain an insight into the bone marrow environment change after osteocyte ablation, single cell RNA sequencing (scRNA-seq) was performed
2022-11-21 | GSE202516 | GEO
Project description:Osteocytes regulate skeletal senescence during development
| PRJNA836422 | ENA
Project description:Osteocytes regulate skeletal senescence during development
| PRJNA835705 | ENA
Project description:Estrogens are well known steroid hormones necessary to maintain bone health. In addition, mechanical loading, which estrogen signaling may intersect with the Wnt/β-catenin pathway, is also essential for bone health. As osteocytes are known as the major mechanosensory cells embedded in mineralized bone matrix, osteocyte ERα deletion mice (ERαΔOcy/ΔOcy) were generated by mating ERα floxed mice with Dmp1-Cre mice to determine functions of ERα in osteocytes. Trabecular bone mineral density of female, but not male ERαΔOcy/ΔOcy mice was significantly decreased. Bone formation parameters in ERαΔOcy/ΔOcy were significantly decreased while osteoclast parameters were unchanged. This suggests that ERα in osteocytes exerts osteoprotective function by positively controlling bone formation. To identify potential targets of ERα, gene array analysis of Dmp1-GFP osteocytes FACS sorted from ERαΔOcy/ΔOcy and control mice was performed. Expression of Mdk and Sostdc1, both known inhibitors of Wnt, were significantly increased without alteration of the mature osteocyte marker Sost or β-catenin. Hindlimb unloading exacerbated the trabecular bone loss, but surprisingly cortical bone was resistant. These studies show that ERα in osteocytes has osteoprotective effects in trabecular bone through regulating expression of Wnt antagonists, but conversely plays a negative role in cortical bone loss due to unloading.
2013-12-12 | GSE41997 | GEO
Project description:Estrogens are well known steroid hormones necessary to maintain bone health. In addition, mechanical loading, which estrogen signaling may intersect with the Wnt/β-catenin pathway, is also essential for bone health. As osteocytes are known as the major mechanosensory cells embedded in mineralized bone matrix, osteocyte ERα deletion mice (ERαÎOcy/ÎOcy) were generated by mating ERα floxed mice with Dmp1-Cre mice to determine functions of ERα in osteocytes. Trabecular bone mineral density of female, but not male ERαÎOcy/ÎOcy mice was significantly decreased. Bone formation parameters in ERαÎOcy/ÎOcy were significantly decreased while osteoclast parameters were unchanged. This suggests that ERα in osteocytes exerts osteoprotective function by positively controlling bone formation. To identify potential targets of ERα, gene array analysis of Dmp1-GFP osteocytes FACS sorted from ERαÎOcy/ÎOcy and control mice was performed. Expression of Mdk and Sostdc1, both known inhibitors of Wnt, were significantly increased without alteration of the mature osteocyte marker Sost or β-catenin. Hindlimb unloading exacerbated the trabecular bone loss, but surprisingly cortical bone was resistant. These studies show that ERα in osteocytes has osteoprotective effects in trabecular bone through regulating expression of Wnt antagonists, but conversely plays a negative role in cortical bone loss due to unloading. Wild type and osteocyte-specific Estrogen Receptor alpha knock-out mice were generated. The number of both genotypes of mice was three. Calvarial osteocytes of both genotypes harboring Dmp1-GFP were extracted by sequential enzymatic digestion, followed by FACS Aria sorting and total RNAs were purified for Affymetix GeneChip microarray analysis without pooling.
2013-12-12 | E-GEOD-41997 | biostudies-arrayexpress
Project description:Using oligomycin A-treated MLO-Y4 cells and primary murine aging osteocytes as a model of cells with mitochondrial dysfunction, it is demonstrated that when mitochondria are damaged, osteocytes tend to release signaling compounds including adenosine diphosphate. We identified that the nucleotide membrane receptors P2Y2 and P2Y6 transduced the ADP signal to Mfn2, a critical regulator of osteocyte mitochondrial transfer. Whole RNA sequencing (RNA-seq) analysis of mouse cortical bone showed that mitochondrial metabolism is impaired in aged osteocytes, and there are more extracellular nucleotides released into the matrix in cortical bone in aged mice as compared to that in young mice. Aging decreases expression levels of P2Y2/P2Y6 and Mfn2.
2024-01-24 | GSE235103 | GEO
Project description:The main reservoir for Staphylococcus aureus osteomyelitis is the bone tissue where this pathogen can persist and form small colony variants for long periods within osteoblasts and osteocytes. Recently the osteocytes were described as a main reservoir for this pathogen in bone tissue. However, the mechanisms involved in the persistence of S. aureus within these cells are still unknown. Here we investigated the intrinsic relation between S. aureus and both bone cells during infection. The infection of osteoblasts and osteocytes by this pathogen generates the functional bifurcation of these cells into two different responders. Whereas osteoblasts are able to induce a strong antimicrobial respond, the osteocytes trigger signals to recruit immune cells and enhance the inflammation. Moreover, we found that extracellular signals from osteocytes enhance the intracellular bacterial clearance on osteoblasts but not on osteocytes. Even that both cells contain TLR2, the main toll receptor responsible of S. aureus recognition, only osteoblasts were able to increase its expression after infection. Although the expression of TLR2 was not altered in osteocytes, these cells secrete higher lipid mediators and cytokines than osteoblasts. In addition, we found by proteomic analysis that the reduced intracellular bacterial killing of osteocytes is related to a low expression of antimicrobial peptides and reactive oxygen species (ROS) in these cells. Our results suggest that osteocytes contribute to the high inflammation observed in osteomyelitis and at the same time, provide the main niche for S. aureus persistence due to their poor intracellular antimicrobial response. Collectively, these findings reveal the roles of bone cells upon S. aureus infection and provide new insight on the treatment failure of osteomyelitis.
2022-08-02 | PXD029440 | Pride
Project description:Fibroblast growth factor 23 (FGF23), a hormone, mainly produced by osteocytes, regulates phosphate and vitamin D metabolism. By contrast, 1,25-dihydroxyvitamin D3, the active form of vitamin D, has been shown to enhance FGF23 production. While it is likely that osteocytes are heterogenous in terms of gene expression profiles, specific subpopulations of Fgf23-expressing osteocytes have not been identified. Single-cell RNA sequencing (scRNA-seq) technology can characterize the transcriptome of an individual cell. Recently, scRNA-seq has been used for bone tissue analysis. However, owing to technical difficulties associated with isolation of osteocytes, studies using scRNA-seq analysis to characterize FGF23-producing osteocytes are lacking. In this study, we characterized osteocytes secreting FGF23 from murine femurs in response to calcitriol (1,25-dihydroxyvitamin D3) using scRNA-seq. We first detected Dmp1, Mepe, and Phex expression in murine osteocytes by in situ hybridization and used these as marker genes of osteocytes. After decalcification, enzyme digestion, and removal of CD45+ cells, femoral bone cells were subjected to scRNA-seq. We identified cell clusters containing osteocytes using marker gene expression. While Fgf23 expression was observed in some osteocytes isolated from femurs of calcitriol-injected mice, no Fgf23 expression was detected in untreated mice. In addition, the expression of several genes which are known to be changed after 1,25-dihydroxyvitamin D3 treatment such as Ccnd2, Fn1, Igfbp7, Pdgfa, and Timp1 was also affected by calcitriol treatment in Fgf23-expressing osteocytes, but not in those lacking Fgf23 expression, even after calcitriol administration. Furthermore, box-and-whisker plots indicated that Fgf23 expression was observed in osteocytes with higher expression levels of the Fam20c, Dmp1, and Phex genes, whose inactivating mutations have been shown to cause FGF23-related hypophosphatemic diseases. These results indicate that osteocytes are heterogeneous with respect to their responsiveness to 1,25-dihydroxyvitamin D3, and sensitivity to 1,25-dihydroxyvitamin D3 is one of the characteristics of osteocytes with Fgf23 expression. It is likely that there is a subpopulation of osteocytes expressing several genes, including Fgf23, involved in phosphate metabolism.
2022-12-17 | GSE220836 | GEO
Project description:Jason M. Graham, Bruce P. Ayati, Sarah A. Holstein & James A. Martin. The role of osteocytes in targeted bone remodeling: a mathematical model. PLoS ONE 8, 5 (2013).
Until recently many studies of bone remodeling at the cellular level have focused on the behavior of mature osteoblasts and osteoclasts, and their respective precursor cells, with the role of osteocytes and bone lining cells left largely unexplored. This is particularly true with respect to the mathematical modeling of bone remodeling. However, there is increasing evidence that osteocytes play important roles in the cycle of targeted bone remodeling, in serving as a significant source of RANKL to support osteoclastogenesis, and in secreting the bone formation inhibitor sclerostin. Moreover, there is also increasing interest in sclerostin, an osteocyte-secreted bone formation inhibitor, and its role in regulating local response to changes in the bone microenvironment. Here we develop a cell population model of bone remodeling that includes the role of osteocytes, sclerostin, and allows for the possibility of RANKL expression by osteocyte cell populations. We have aimed to give a simple, yet still tractable, model that remains faithful to the underlying system based on the known literature. This model extends and complements many of the existing mathematical models for bone remodeling, but can be used to explore aspects of the process of bone remodeling that were previously beyond the scope of prior modeling work. Through numerical simulations we demonstrate that our model can be used to explore theoretically many of the qualitative features of the role of osteocytes in bone biology as presented in recent literature.
2024-09-02 | BIOMD0000000721 | BioModels
Project description:We have previously shown that during lactation, osteocytes directly remodel their perilacunar and pericanalicular matrix, thereby mobilizing calcium and contributing to maternal bone loss. To identify genes potentially responsible for perilacunar remodeling, microarray analysis was performed on osteocytes from CD-1 virgin and lactating mice and mice sacrificed on day 7 post weaning. By comparing how gene expression changes in osteocytes among virgin, lactation and post lactation, the goal is to identify the genes osteocytes use to remodel their perilacunar matrix
2011-12-31 | GSE23496 | GEO