Osteocytes regulate skeletal senescence during development
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE202516 | GEO | 2022/11/21
REPOSITORIES: GEO
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Project description:To understand the mechanism underlying the bone phenotype in osteocytes ablation mice.
2022-11-21 | GSE202356 | 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 (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: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: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 To identify genes responsible for perilacunar remodeling, microarray analysis was performed on tibiae from CD-1 virgin and lactating mice and mice sacrificed on day 7 post weaning. Periosteum and bone marrow were removed from the tibiae and the bone fragments underwent sequential collagenase/trypsin digestion and were examined histologically to ensure removal of all surface cells and confirm osteocyte enrichment prior to RNA extraction. Microarray Affy M430 arrays, n=3 per group were performed and Genepattern and Bioconductor were used to analyse the microdata.
2011-12-31 | E-GEOD-23496 | biostudies-arrayexpress
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:The involvement of osteocytes in multiple myeloma (MM)-induced osteoclast formation and the occurrence of bone lesions are still unknown. Osteocytes regulate bone remodeling at least in part through the cell death and apoptosis triggering osteoclast recruitment and formation. In this study, firstly we shown that MM cells increased osteocyte death and affect their transcriptional profile evaluated by microarray analysis up-regulating osteoclastogenic cytokines as interleukin (IL)-11. Consistently we show that the conditioned media of human pre-osteocytes co-cultured with MM cells significantly increased osteoclastogenesis. To translate into a clinical perspective such in vitro evidences, we then performed histological analysis on bone biopsies obtained from MM patients, MGUS and healthy controls. We found a significant reduction in the number of viable osteocytes in MM patients as compared to controls. A significant negative correlation between the number of viable osteocytes and that of osteoclasts was also demonstrated. Moreover, as regards the skeletal involvement, we found that MM patients with bone lesions have a significant lower number of viable osteocyte than those without. Overall, our data suggest a role of osteocytic cell death in MM-induced osteoclast formation in vitro and MM bone disease in vivo in MM patients.
2012-05-22 | GSE27372 | GEO
Project description:Although localized to the mineralized matrix of bone, osteocytes are able to respond to systemic factors such as the calciotropic hormones 1,25(OH)2D3 and PTH. In the present studies, we examine the transcriptomic response to PTH in an osteocyte cell model and found that this hormone regulated an extensive panel of genes. Surprisingly, PTH uniquely modulated two cohorts of genes, one that was expressed and associated with the osteoblast to osteocyte transition and the other a cohort that was expressed only in the mature osteocyte. Interestingly, PTH’s effects were largely to oppose the expression of differentiation-related genes in the former cohort, while potentiating the expression of osteocyte-specific genes in the latter cohort. A comparison of the transcriptional effects of PTH with those obtained previously with 1,25(OH)2D3 revealed a subset of genes that was strongly overlapping. While 1,25(OH)2D3 potentiated the expression of osteocyte-specific genes similar to that seen with PTH, the overlap between the two hormones was more limited. Additional experiments identified the PKA-activated phospho-CREB (pCREB) cistrome, revealing that while many of the differentiation-related PTH regulated genes were apparent targets of a PKA-mediated signaling pathway, a reduction in pCREB binding at sites associated with osteocyte-specific PTH targets appeared to involve alternative PTH activation pathways. That pCREB binding activities positioned near important hormone-regulated gene cohorts were localized to control regions of genes was reinforced by the presence of epigenetic enhancer signatures exemplified by unique modifications at histones H3 and H4. These studies suggest that both PTH and 1,25(OH)2D3 may play important and perhaps cooperative roles in limiting osteocyte differentiation from its precursors while simultaneously exerting distinct roles in regulating mature osteocyte function. Our results provide new insight into transcription factor-associated mechanisms through which PTH and 1,25(OH)2D3 regulate a plethora of genes important to the osteoblast/osteocyte lineage. ChIP-seq was performed on MC3T3-E1 cells for Phospho-Creb following 1 hour vehicle or forskolin treatment in biological replicate. Input sample was previously published in GSE41920 (http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM1027508).
2014-11-14 | E-GEOD-62978 | biostudies-arrayexpress
Project description:Although localized to the mineralized matrix of bone, osteocytes are able to respond to systemic factors such as the calciotropic hormones 1,25(OH)2D3 and PTH. In the present studies, we examine the transcriptomic response to PTH in an osteocyte cell model and found that this hormone regulated an extensive panel of genes. Surprisingly, PTH uniquely modulated two cohorts of genes, one that was expressed and associated with the osteoblast to osteocyte transition and the other a cohort that was expressed only in the mature osteocyte. Interestingly, PTHM-bM-^@M-^Ys effects were largely to oppose the expression of differentiation-related genes in the former cohort, while potentiating the expression of osteocyte-specific genes in the latter cohort. A comparison of the transcriptional effects of PTH with those obtained previously with 1,25(OH)2D3 revealed a subset of genes that was strongly overlapping. While 1,25(OH)2D3 potentiated the expression of osteocyte-specific genes similar to that seen with PTH, the overlap between the two hormones was more limited. Additional experiments identified the PKA-activated phospho-CREB (pCREB) cistrome, revealing that while many of the differentiation-related PTH regulated genes were apparent targets of a PKA-mediated signaling pathway, a reduction in pCREB binding at sites associated with osteocyte-specific PTH targets appeared to involve alternative PTH activation pathways. That pCREB binding activities positioned near important hormone-regulated gene cohorts were localized to control regions of genes was reinforced by the presence of epigenetic enhancer signatures exemplified by unique modifications at histones H3 and H4. These studies suggest that both PTH and 1,25(OH)2D3 may play important and perhaps cooperative roles in limiting osteocyte differentiation from its precursors while simultaneously exerting distinct roles in regulating mature osteocyte function. Our results provide new insight into transcription factor-associated mechanisms through which PTH and 1,25(OH)2D3 regulate a plethora of genes important to the osteoblast/osteocyte lineage. Fully differentiated IDG-SW3 cells were treated in biological triplicate with 100nM PTH for 24 hours prior to mRNA isolation and sequencing. Vehicle treated samples were previously published in GSE54783: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM1323967 http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM1323968 http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM1323969
2014-11-14 | E-GEOD-62979 | biostudies-arrayexpress