Transcriptional regulation of jaw osteoblasts: development to pathology
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE186535 | GEO | 2022/02/14
REPOSITORIES: GEO
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Project description:Certain bone graft materials are employed for alveolar bone regeneration, and autografts are commonly used. Alveolar and jaw bones are developmentally derived from neural crest cells, while most trunk and limb bones are derived from mesodermal mesenchymal cells. Consequently, the chosen bone graft material is likely to have a different developmental origin than the recipient bone. We hypothesized that there are differences in the gene expression profiles and bone healing capacities between bones with different developmental origins. Therefore, we investigated these properties in the maxilla, mandible, ilium and femur. DNA microarray data revealed close homology between the gene expression profiles of the ilium and femur. The gene expressions of Wnt-1, P75, SOX10, Nestin and Musashi-1 were significantly higher in the maxilla and mandible than in the ilium and femur. The frontal bone healed faster than the parietal bone. Parietal bone defects transplanted with maxillary and mandibular bone grafts exhibited closure. Thus, it is suggested that the maxilla and mandible have different gene expression profiles from the other bones examined, and exhibit neural crest cell properties with a marked healing ability in adults. The data further suggest that jaw bones are effective as both bone graft materials and graft beds.
2011-06-30 | GSE30167 | GEO
Project description:The reciprocal interaction between cancer cells and the tissue-specific stroma is critical for primary and metastatic tumor growth progression. Prostate cancer cells colonize preferentially bone (osteotropism), where they alter the physiological balance between osteoblast-mediated bone formation and osteoclast-mediated bone resorption, and elicit prevalently an osteoblastic response (osteoinduction). The molecular cues provided by osteoblasts for the survival and growth of bone metastatic prostate cancer cells are largely unknown. We exploited the sufficient divergence between human and mouse RNA sequences together with redefinition of highly species-specific gene arrays by computer-aided and experimental exclusion of cross-hybridizing oligonucleotide probes. This strategy allowed the dissection of the stroma (mouse) from the cancer cell (human) transcriptome in bone metastasis xenograft models of human osteoinductive prostate cancer cells (VCaP and C4-2B). As a result, we generated the osteoblastic bone metastasis-associated stroma transcriptome (OB-BMST). Subtraction of genes shared by inflammation, wound healing and desmoplastic responses, and by the tissue type-independent stroma responses to a variety of non-osteotropic and osteotropic primary cancers generated a curated gene signature (“Core” OB-BMST) putatively representing the bone marrow/bone-specific stroma response to prostate cancer-induced, osteoblastic bone metastasis. The expression pattern of three representative Core OB-BMST genes (PTN, EPHA3 and FSCN1) seems to confirm the bone specificity of this response. A robust induction of genes involved in osteogenesis and angiogenesis dominates both the OB-BMST and Core OB-BMST. This translates in an amplification of hematopoietic and, remarkably, prostate epithelial stem cell niche components that may function as a self-reinforcing bone metastatic niche providing a growth support specific for osteoinductive prostate cancer cells. The induction of this combinatorial stem cell niche is a novel mechanism that may also explain cancer cell osteotropism and local interference with hematopoiesis (myelophthisis). Accordingly, these stem cell niche components may represent innovative therapeutic targets and/or serum biomarkers in osteoblastic bone metastasis. Keywords: cancer, transcription-profile, bone, metastasis, stroma 3 samples of VCaP xenografted mouse bones (VCaP xenografts 1/2/3), 3 samples of C4-2B xenografted mouse bones (C4-2B xenografts 1/2/3), 2 samples of Ep156T xenografted mouse bones (Ep156T xenografts 1/2), 2 samples of sham-operated mouse bones (sham-operated bones 1/2) and 3 samples of intact mouse bones (intact bones 1/2/3) were profiled on Affymetrix Mouse Genome 430A 2.0 Arrays. Sample code: MVX stands for VCaP xenografts, MBM for Intact bone samples, MCX for C4-2B xenografts and MNX for Sham-operated bones samples
2014-12-09 | E-GEOD-22813 | biostudies-arrayexpress
Project description:Transcriptional regulation of jaw osteoblasts: development to pathology
| PRJNA774327 | ENA
Project description:The jaws are complementary in form and function but develop asymmetrically, as the lower but not upper jaw bone forms around a prominent cartilage template. How such differences in skeletal composition are patterned is unclear. Here, we identify four Nuclear receptor 2f genes, nr2f1a, nr2f1b, nr2f2, and nr2f5, as enriched in zebrafish upper jaw precursors. Whereas loss of Nr2f genes results in expansion of upper jaw cartilage to resemble that of the lower jaw, Nr2f5 misexpression inhibits lower jaw cartilage formation. Genome-wide analyses show that Nr2f genes prevent expansion of lower jaw-associated gene expression into the upper jaw territory. Further, restriction of Nr2f expression by Endothelin1 signaling is critical for lower jaw development, as reducing Nr2f dosage fully restores lower jaw development in edn1 mutants. We propose that Nr2f genes drive jaw asymmetry by limiting early cartilage differentiation in the upper jaw to preserve more precursors for later osteogenesis.
2018-01-18 | GSE101719 | GEO
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:The functional jaw is composed of multiple connective tissues including skeletal components (bone, cartilage, and teeth), tendon, ligament, and musculature. Cranial neural crest-derived mesenchyme of the mandibular arch give rise to diverse tissue types within the lower jaw. To understand how the specification of diverse cell types with spatial and temporal precision is achieved, we profile multi-omic chromatin accessibility (snATACseq) and transcriptome (snRNAseq) of jaw mesenchyme at single-cell resolution from the developing zebrafish jaw.
2023-02-13 | GSE210251 | GEO
Project description:Ossifying fibroma (OF) is a common benign fibro-osseous neoplasm of orofacial bones, showing progressive enlargement of the affected jaw with deficiency in bone formation. Our aim is to discover the molecular difference between mesenchymal stem cells from OF and normal jaw bone to provide basis for development of clinical therapy. Global gene expression comparison and gene ontology analysis found that several singaling pathways are involved in the process, including TGFb signaling and Notch signaling. Inhibition of TGFb signaling in mesenchymal stem cells of OF can increase the osteogenesis and decrease proliferation, shedding light on developing strategies for therapy. RNA from mesenchymal stem cells of OF is compared to that of normal jaw bone.
2013-07-24 | E-GEOD-49165 | biostudies-arrayexpress
Project description:Objective: Craniofacial bone defects caused by injuries and congenital diseases are a formidable challenge to clinicians. Research has shown promise in using bone marrow mesenchymal stem cells (BM-MSCs) from limb bones for craniofacial bone regeneration; yet little is known about the potential of BM-MSCs from craniofacial bones. This study compared BM-MSCs isolated from limb and craniofacial bones in pigs, a preclinical model closely resembling humans. Design: Bone marrow was aspirated from the tibia and mandible of four-month-old pigs (n=4), followed by BM-MSC isolation, culture-expansion and confirmation by flow cytometry. Proliferation rates were compared using population doubling times. Osteogenic differentiation was evaluated by quantifying alkaline phosphatase (ALP) activity. Total mRNA was extracted from freshly isolated BM-MSCs and analyzed to compare gene expressions of tibial and mandibular BM-MSCs using an Affymetrix GeneChip porcine genome array, followed by real-time RT-PCR evaluation of two neural crest markers. Results: BM-MSCs from both locations expressed MSC markers without expression of hematopoietic markers. Mandibular BM-MSCs proliferated significantly faster than tibial BM-MSCs. Without osteogenic inducers, mandibular BM-MSC alkaline phosphatase activities were 3.3-fold greater than those of tibial origin. Microarray analysis identified 383 differentially expressed genes in mandibular and tibial BM-MSCs, including higher expression of cranial neural crest-related genes nestin and BMP-4 in mandibular BM-MSCs, a trend also confirmed by real-time RT-PCR. Among differently expressed genes, only 47 showed greater than 1.5-fold differences in expression. Conclusions: These data indicate that despite many similarities in gene expression, mandibular BM-MSCs express of number of genes differently than tibial BM-MSCs and have a phenotypic profile that may make them advantageous for craniofacial bone regeneration. Bone marrow was aspirated from the mandibular symphyseal region and the tibia of 3 pigs. Mesenchymal stem cells were isolated from the bone marrow and cultured to 80% confluence. Cells were harvested for total RNA extraction and the RNA was analyzed by Affymetrix GeneChip porcine genome array.
2016-05-14 | E-GEOD-81430 | biostudies-arrayexpress
Project description:Analysis of gene expression in activation-tagged jaw-d mutant plants. Total RNA was extracted from the aerial parts of two weeks old jaw-d and control plants. Keywords: other
2003-07-09 | GSE518 | GEO
Project description:Objectives: Osteonecrosis of the jaw (ONJ), a necrotic bone disease unique to the craniofacial region, is often observed among cancer patients treated with bisphosphonate (BP)-based chemotherapy and becomes a costly and debilitating source of pain and reduced quality of life. Elucidation of clinicopathological mechanism and biomarkers of ONJ that can indicate probable disease course would allow for better assessment of treatment strategies for individual patients. To address our overall goal of identifying novel diagnostic and prognostic strategies for ONJ, this study specifically aims to understand the alendronate (ALN) treatment-induced perturbation of bone proteome and microenvironmental pathophysiology of ONJ using targeted molecular analyses and computational approaches based on an in vitro cell culture system. This study also focuses on identifying proteome perturbation and potential molecular biomarkers during ONJ development. Methods: To understand the molecular mechanisms underlying ONJ, an unbiased and global proteomics approach combined with big data analysis using bioinformatics was applied. Biochemical and functional analyses were followed to tease out the mechanisms regulated by ALN treatment. Results: The current findings from our global proteomics study and biochemical analyses suggested that the RIPK3/Wnt/GSK3/β-catenin signaling pathway is significantly perturbed upon alendronate treatment, resulting in abnormal angiogenesis/inflammation/bone anabolism/remodeling/bone mineralization in the in vitro cell culture system. Conclusion: This investigation on potential key signaling mechanisms underlying ONJ will provide a rational basis for suppressing BP-induced ONJ and novel therapeutic strategies against ONJ.
2021-09-10 | PXD024585 | Pride