Physiological transcriptional profiling of murine osteocytes from calvaria and long bones
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE199176 | GEO | 2025/03/22
REPOSITORIES: GEO
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Project description:Purpose: This study investigates the postnatal impact of Twist1 haploinsufficiency on the osteoskeletal ability and regeneration on two calvarial bones arising from tissues of different embryonic origin: the neural crest-derived frontal and the mesoderm-derived parietal bones. Results: Twist1 haplonsufficiency selectively enhanced osteogenic and tissue regeneration ability of mesoderm-derived parietal bones. Twist1 haplonsufficiency triggers its selective activity on mesoderm-derived parietal bone through downregulation of the bone-derived hormone Fgf23. Conclusions: Twist1 haploinsufficiency preferentially triggers osteogenic induction of parietal bones which may be beneficial to optimize treatments for skeletal regeneration, reconstruction and repair of mesoderm-derived bone, as well as to alleviate skeletal abnormalities caused by Twist1 haploinsufficiency.
2018-09-15 | GSE119962 | 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:There are three main cell types associated with the skeleton, osteoblasts that bone build, osteoclasts that resorb bone and the osteocytes which among other things control the action of these other effector cell types. In this experiment we compare transcriptome data from bone samples enriched for osteocytes (by removing soft tissue and marrow) and bone samples with the soft tissue removed but the marrow left intact. This identifies genes that are enriched for data when we enrich for osteocytes - highlighting genes enriched for expression in this pivotal skeletal cell type.
2020-03-04 | E-MTAB-5533 | biostudies-arrayexpress
Project description:Previous investigations suggest that the different embryonic origins of the calvarial tissues (neural crest or mesoderm) may account for the different molecular mechanisms underlying sutural development. The aim of this study was to evaluate the differences in the gene expression of human cranial tissues and assess the presence of an expression signature reflecting their embryonic origins. Using microarray technology, we investigated global gene expression of cells from the frontal and parietal bones and the metopic and sagittal intrasutural mesenchyme (ISM) of four human fetal calvaria. Tissues samples were obtained from fetal crania of 4 normal human fetuses (two females ages 94 and 103 days and two males ages 97 and 98 days). All dural and extracranial soft tissues were removed from the parietal and frontal bones. 2-3 mm tissue compartments were excised from frontal and parietal bones and metopic and sagittal ISM. To avoid contamination with osteoblasts, ISM tissue was dissected from the central portion of each suture. Similarly, bone was harvested at least 3mm from the margin of the suture to avoid contamination with ISM. Media was changed every 3-4 days. After reaching 75-80% confluence, the cells were trypsinized with TrypLEExpress (Life Technologies, Denmark) and passaged. During the fourth and final passage, 180,000 cells were plated in triplicate in 6-well plates and cultured for 5 days followed by RNA extraction.
2015-08-03 | E-GEOD-62816 | biostudies-arrayexpress
Project description:Local site-specific differences between bones in different regions of the skeleton account for their different properties and functions. To identify mechanisms behind these differences, we have performed a cross-species study comparing RNA transcriptomes of cranial and tibial osteocytes, from bones with very different primary functions and physiological responses, collected from the same individual mouse, rat and rhesus macaque. Bioinformatic analysis was performed to identify 32 genes changed in the same direction between sites and shared across all three species. Several well-established key genes in bone growth and remodelling were upregulated in the tibias of all three species (BMP7, DKK1, FGF1, FRZB, SOST). Many of them associate or crosstalk with the canonical Wnt signalling pathway. These results suggest Wnt signalling-related candidates for different control of regulatory mechanisms in bone homeostasis in the skull and tibia and indicate a different balance between genetically determined structure and feedback mechanisms to strains induced by mechanical loading at the different sites.
2020-07-08 | GSE151971 | GEO
Project description:Skeletal tissue is known to respond to mechanical stress. Ultrasound stimulation is one of mechanical stress and low intensity pulsed ultrasound (LIPUS) devices have been clinically utilized to promote the fracture healing. However, it is still not clear which skeletal cells, especially osteocytes or osteoblasts, mainly respond to LIPUS stimulation and how they contribute to fracture healing. To examine that, we utilized medaka known to have bones without embedded osteocytes and zebrafish known to have bones with embedded osteocytes as an in vivo model. Interestingly, fracture healing was accelerated by ultrasound stimulation in zebrafish but not in medaka. To examine the molecular events induced by LIPUS stimulation in osteocyte, we performed RNA-sequencing with the murine long bone osteocyte Y4 (MLO-Y4) cell line exposed to LIPUS. 179 genes reacted to LIPUS stimulation and functional cluster analysis defined that several molecular signatures related in immunity, secretion and transcription. Especially, most of isolated transcription related genes were modulated by LIPUS also in vivo experiments using zebrafish. Target genes analysis showed that inflammatory response and bone formation in fracture healing could be transcriptionally regulated in osteocytes by LIPUS stimulation. Among these transcription genes, early growth response (Egr) 1,2, JunB, Forkhead box Q1 (FoxQ1) and nuclear factor of activated T cells (NFAT) c1 were not altered by LIPUS in medaka unlike zebrafish suggesting that these genes would be key transcriptional regulator of LIPUS-dependent fracture healing through osteocytes. In this study, we revealed bone-equipped osteocytes is necessary for LIPUS-induced promotion of fracture healing through the transcriptional control of target genes presumably to activate neighboring cells involved in fracture healing event.
2021-05-03 | GSE162674 | 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:Mesenchymal stem cells (MSCs) And osteolineage cells contribute to the hematopoietic stem cell (HSC) Niche in the bone marrow of long bones. However, Their developmental relationships remain unclear. Here we demonstrate that different MSC populations in the developing marrow of long bones have distinct functions. Proliferative mesoderm-derived nestin- MSCs participate in fetal skeletogenesis, And lose MSC activity soon after birth. In contrast, Quiescent neural-crest-derived nestin+ Cells in the same bones preserve MSC activity, But do not generate fetal chondrocytes. Instead, They differentiate into HSC-niche-forming MSCs, Helping to establish the HSC niche by secreting Cxcl12. Perineural migration of these cells to the bone marrow requires the ErbB3 receptor. The neonatal Nestin-GFP+ PDGFR- Cell population also contains Schwann-cell precursors, But does not comprise mature Schwann cells. Thus, In the developing bone marrow HSC-niche-forming MSCs share a common origin with sympathetic peripheral neurons and glial cells, And ontogenically distinct MSCs have non-overlapping functions in endochondrogenesis and HSC niche formation. Total RNA was isolated from small numbers of FACS sorted stromal cells, obtained from neonatal Nes-Gfp bone marrow preparations (2 biological replicates). Each independent set of samples was obtained from pooled skeletal elements (long bones and sterna) form multiple littermates.
2014-10-15 | E-GEOD-61695 | biostudies-arrayexpress
Project description:Purpose of arrays were to determine what the effect of deletion of Mbtps1 gene was on gene expression of osteocytes in bone in vivo. DMP1 cre driver was used to delete the Mbtps1 gene in osteocytes and osteoblasts in bone. We then isolated osteocyte enriched bone particles from 40 week old male mice to determine the effect of this deletion on gene expression. We have previously shown that Mbtps1 is needed for transcription of Phex, DMP1, and MEPE genes in osteoblasts in culture. Arrays showed these genes were reduced as expected in osteocytes in vivo. Controls represent osteocyte enriched bone from 40 week old littermates. Also, as expected, Mbtps1 expression was reduced in these knockout mice
2015-12-29 | GSE69975 | GEO
Project description:Mesenchymal stem cells (MSCs) And osteolineage cells contribute to the hematopoietic stem cell (HSC) Niche in the bone marrow of long bones. However, Their developmental relationships remain unclear. Here we demonstrate that different MSC populations in the developing marrow of long bones have distinct functions. Proliferative mesoderm-derived nestin- MSCs participate in fetal skeletogenesis, And lose MSC activity soon after birth. In contrast, Quiescent neural-crest-derived nestin+ Cells in the same bones preserve MSC activity, But do not generate fetal chondrocytes. Instead, They differentiate into HSC-niche-forming MSCs, Helping to establish the HSC niche by secreting Cxcl12. Perineural migration of these cells to the bone marrow requires the ErbB3 receptor. The neonatal Nestin-GFP+ PDGFR- Cell population also contains Schwann-cell precursors, But does not comprise mature Schwann cells. Thus, In the developing bone marrow HSC-niche-forming MSCs share a common origin with sympathetic peripheral neurons and glial cells, And ontogenically distinct MSCs have non-overlapping functions in endochondrogenesis and HSC niche formation.
2014-10-15 | GSE61695 | GEO