Transcriptome analysis of the mandibles from FcgRIIB-deficient mouse model of lupus
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE179155 | GEO | 2021/09/29
REPOSITORIES: GEO
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Project description:Background Extracellular matrix (ECM) protein malfunction or defect may lead to temporomandibular joint osteoarthritis (TMJ OA). Dentin sialophophoprotein (DSPP) is a mandibular condylar cartilage ECM protein, and its deletion impacted cell proliferation and other extracellular matrix alterations of postnatal condylar cartilage. However, it remains unclear if long-term loss of function of DSPP leads to TMJ OA. The study aimed to test the hypothesis that long-term haploinsufficiency of DSPP causes TMJ OA. Materials and Methods To determine whether Dspp+/- mice exhibit TMJ OA but no severe tooth defects, mandibles of wild-type (WT), Dspp+/-, and Dspp homozygous (Dspp-/-) mice were analyzed by Micro-computed tomography (micro-CT). To characterize the progression and possible mechanisms of osteoarthritic degeneration over time in Dspp+/- mice over time, condyles of Dspp+/- and WT mice were analyzed radiologically, histologically, and immunohistochemically. Results Micro-CT and histomorphometric analyses revealed that Dspp+/- and Dspp-/- mice had significantly lower subchondral bone mass, bone volume fraction, bone mineral density, and trabecular thickness compared to WT mice at 12 months. Interestingly, in contrast to Dspp-/- mice which exhibited tooth loss, Dspp+/- mice had minor tooth defects. RNA sequencing data showed that haplodeficency of DSPP affects the biological process of ossification and osteoclast differentiation. Additionally, histological analysis showed that Dspp+/- mice had condylar cartilage fissures, reduced cartilage thickness, decreased articular cell numbers and severe subchondral bone cavities, and with signs that were exaggerated with age. Radiographic data showed an increase in subchondral osteoporosis up to 18 months and osteophyte formation at 21 months. Moreover, Dspp+/- mice showed increased distribution of osteoclast in the subchondal bone and increased expression of MMP2, IL-6, FN-1, and TLR4 in the mandibular condylar cartilage. Conclusions Dspp+/- mice exhibit TMJ OA in a time-dependent manner, with lesions in the mandibular condyle attributed to hypomineralization of subchondral bone and breakdown of the mandibular condylar cartilage, accompanied by upregulation of inflammatory markers.
2024-03-19 | GSE261528 | GEO
Project description:We conditionally knocked out both Yap and Taz in cranial neural crest (CNC) using the Wnt1Cre driver and sequenced mRNA from embryonic day 10.5 mandibles. Examination of mRNA level in E10.5 mandibular tissues from control and Wnt1Cre Taz and Yap dKO mutant.
2016-03-01 | E-GEOD-69311 | biostudies-arrayexpress
Project description:Previous analysis of Myf5-/-:MyoD-/- mouse fetuses lacking skeletal muscle demonstrated the importance of muscle contraction and static loading in mouse skeletogenesis. Previous analysis of Myf5-/-:MyoD-/- mouse fetuses lacking skeletal muscle demonstrated the importance of muscle contraction and static loading in mouse skeletogenesis. Among abnormal skeletal features, micrognathia (mandibular hypoplasia) was detected: small, bent and posteriorly displaced mandible. As an example of Waddingtonian epigenetics, we suggest that muscle, in addition to acting via mechanochemical signal transduction pathways, networks and promoters, also exerts secretory stimuli on skeleton. Our goal is to identify candidate molecules at that muscle-mandible interface. By employing Systematic Subtractive Microarray Analysis approach, we compared gene expression between mandibles of amyogenic and wild type mouse fetuses. We identified a set of candidate genes with involvement in mandibulardevelopment: Cacna1s, Ckm, Des, Mir300, Myog and Tnnc1. We also performed mouse-to-human translational experiments and found analogies. In the light of our findings we discuss various players in mandibular morphogenesis and make an argument for the need to consider mandibular development as a consequence of reciprocal epigenetic interactions of both skeletal and non-skeletal compartments.
2018-01-30 | GSE109779 | GEO
Project description:Type 1 diabetes (T1D) is a multifactorial autoimmune disease characterized by the destruction of pancreatic beta (β) cells and resultant hyperglycaemia. Broad knowledge about the genetics, epidemiology, and clinical management of T1D has been achieved, but the cell varieties in the bone marrow during T1D remain poorly understood. Here, we performed a single-cell RNA sequencing analysis of whole bone marrow cells from healthy (group C) and STZ-induced T1D (group D) mice for the first time, presenting a profile of the bone marrow cells and revealing the changes in immune cells in bone marrow. The bone marrow cells in both groups C and D were divided into 12 clusters, and there were 249 differentially expressed genes (DEGs). Compared with group C, the proportion of CD45+ immune cells in group D was not changed much. However, the diversity of CD45+ immune cells between groups C and D were greatly affected. There was a large increase in the proportion of bone marrow neutrophils (BM-neutrophils) and a large decrease in the proportion of B lymphocytes in group D. Furthermore, it was confirmed by X-ray and micro-CT analyses that osteopenia occurred in group D mice. Finally, we investigated the correlation between immune cells and osteopenia. The results of single-cell flow cytometry and correlation analysis showed that the ratio of BM-neutrophils/B lymphocytes was negatively correlated with osteopenia in T1D mice. Thus, precise regulation of the immune cells in the bone marrow may contribute to a better understanding of the treatment of T1D and the prevention of T1D-induced osteopenia.
2021-08-31 | GSE182986 | GEO
Project description:Skeletal mandibular hypoplasia (SMH), one of the common types of craniofacial deformities, seriously affects appearance, chewing, pronunciation, and breathing. Moreover, SMH is prone to inducing obstructive sleep apnea syndrome. We found that brain and muscle ARNT-like 1 (BMAL1), the core component of the molecular circadian oscillator, was significantly decreased in mandibles of juvenile SMH patients. Accordingly, SMH was observed in circadian rhythm-disrupted or BMAL1-deficiency mice. RNA sequencing and protein chip analyses suggested that matrix metallopeptidase 3 (MMP3) is the potential target of BMAL1 during the mandibular developmental process. Interestingly, in juvenile SMH patients, we observed that MMP3 level was increased obviously. Consistently, MMP3 was upregulated during the whole growth period of 3 to 10 weeks in Bmal1-/- mice. Given these findings, we set to characterize the underlying mechanism and found that BMAL1-deficiency enhanced Mmp3 transcription through activating p65 phosphorylation. Together our results provide new insight into the mechanism by which BMAL1 is implicated in the pathogenesis of SMH
2017-11-07 | GSE106586 | GEO
Project description:Single-cell gene expression of mandibular bone marrow cells and mandibular bone marrow cells under the stimulation of apical periodontitis were determined by scRNAseq.
2023-02-11 | GSE212975 | GEO
Project description:In this study, beta-TCP was implanted in dog mandibles, after which the gene expression profiles and signaling pathways were monitored using microarray and Ingenuity Pathways Analysis (IPA). Following the extraction of premolars and subsequent bone healing, betaâTCP was implanted into the artificial osseous defect. Total RNA was isolated from bone tissues and gene expression profiles were examined using microarray analysis. We used microarrays to detail the global programme of gene expression and identified distinct classes of up- and down- regulated genes during this process. Waiting 3 months healing after tooth extraction from beagle dog mandibles, we drilled the holes in the dog mandibles, and implanted without and with beta-TCP. And these dog mandibles were selected for RNA extraction and hybridization on Affymetrix microarrays. After implanting beta-TCP in the dog mandibles 4, 7, 14 days, we selected sample at 3 time points: Control_4d, beta-TCP_4d, Control_7d, beta-TCP_7d, Control_14d, beta-TCP_14d.
2010-10-19 | E-GEOD-24756 | biostudies-arrayexpress
Project description:During vertebrate craniofacial development, the oral epithelium begins as a simple and morphologically homogeneous tissue. It then gives rise to locally complex structures, including the developing teeth, salivary glands, and taste buds. While there is significant knowledge about the molecular mechanisms regulating the morphogenesis of these organs at later stages, how the epithelium is initially patterned and specified to generate diverse cell types and organs remains largely unknown. To elucidate the genetic programs that direct the formation of distinct oral epithelial populations, we conducted single cell RNA-sequencing using mandibular epithelia from embryonic day (E) 12.0 mouse embryos and whole mandibles from E9.5 mouse embryos. The goal of this study is therefore to generate a detailed transcriptional atlas of the developing mandibular epithelium.
2022-05-27 | GSE202921 | GEO
Project description:Recently, there is increasing report of bone necrosis exceptionally in jaw bone areas after long term administration of anti-resorptive agent, bisphosphonate (BP). It is still unknown that why BP does not result in osteonecrosis but potentiate fracture repair in axial skeleton such as long bones. Many reports had shown that mandibular bone or calvarial bone exhibits lesser resoption than iliac bone graft for maxillofacial bone defect.(Jackson et al 1986, Koole et al 1989),(Crespi et al 2007) These might be attributed to the embryological difference between the two different type of the bone; intramembranous versus endochondral bone formation. Maxilla and mandibular alveolar and basal bone are originated from neural crest cells and exhibit intramembranous bone formation.(Chai and Maxson 2006) However, axial skeleton such as iliac or tibial bones are originated from mesoderm and undergo endochondral bone formation.(Helms and Schneider 2003) It had been reported that there is distinct phenotype difference in human bone cells from different skeletal origin.(Akintoye et al 2006, Kasperk et al 1997),(Matsubara et al 2005) Akintoye et al.(Akintoye et al 2006) reported that mandibular bone marrow stromal cells (BMSCs) displayed a fibroblast-like morphology similar to iliac BMSCs in histological appearance. However, mandibular bone contained less red marrow and hematopoietic cells, whereas the iliac bone contained more red marrow thereby contributing more to hematopoiesis. This differential capacity of mandibular BMSCs with less hematopoietic stem cells is better than that of iliac BMSCs because mitosis in hematopoietic stem cells is usually stopped. They also reported that maxillofacial BMSCs shows higher proliferation rate and alkaline phosphotase activity.(Akintoye et al 2006, Akintoye et al 2008) However, in vivo response of human BMSCs to osteogenic induction was higher in iliac bone than maxillomandibular bone.(Akintoye et al 2006) Other reports had shown that BMSCs from mandible showed better in vitro and in vivo bone formation capacity compared to tibia from rats.(Aghaloo et al 2010) Matsubara et al. reported that osteogenic potential of human or canine alveolar bone and iliac bone-derived cells (BC) are similar but showed difference in chondrogenic and adipogenic potential.(Matsubara et al 2005) From the previous studies, the site-related difference of mandibular and iliac BC are clear. However, the pattern of the site-specificity are not exactly same among above mentioned studies. These might be attributed to the difference in the experimental subjects (species, age) and study design (in-patient or random comparison, etc). Moreover, underlying genetic mechanism of these skeletal-site dependent difference had not been fully investigated. The investigation of site-specific differences in the gene expression would be help to understand the mechanism of bisphosphonate-related osteonecrosis of the jaw (BRONJ), which recently has become an major issue in dentistry. Considering that bisphosphonate is frequently prescribed to elderly patients who have a higher risk of osteoporosis, it is necessary to conduct a experimental analysis of cells from older-aged donors. It had been suggested that anatomical site-specific difference can be influenced by 1) difference in the regional blood supply, 2) difference in bone composition (lamellar bone versus trabecular bone), 3) difference in physiological strain exerted to bone, 4) difference in gene expression according to skeletal site.(Kasperk et al 1997) In this study, bone cells derived from elderly donors went through microarray analysis under the hypothesis that there would be the differences in gene expressions involved in bone formation or cell proliferation of bone cells from iliac and mandible. The purpose of this study was to investigate the difference in gene expression between the human mandible and iliac bone so that we can understand the genetic difference in the two different type of bones. <<<References>>> 1. Jackson IT, Helden G, Marx R. Skull bone grafts in maxillofacial and craniofacial surgery. J Oral Maxillofac Surg 1986; 44:949-955. 2. Koole R, Bosker H, van der Dussen FN. Late secondary autogenous bone grafting in cleft patients comparing mandibular (ectomesenchymal) and iliac crest (mesenchymal) grafts. J Craniomaxillofac Surg 1989; 17 Suppl 1:28-30. 3. Crespi R, Vinci R, Cappare P, Gherlone E, Romanos GE. Calvarial versus iliac crest for autologous bone graft material for a sinus lift procedure: a histomorphometric study. Int J Oral Maxillofac Implants 2007; 22:527-532. 4. Chai Y, Maxson RE, Jr. Recent advances in craniofacial morphogenesis. Dev Dyn 2006; 235:2353-2375. 5. Helms JA, Schneider RA. Cranial skeletal biology. Nature 2003; 423:326-331. 6. Kasperk C, Helmboldt A, Borcsok Iet al. Skeletal site-dependent expression of the androgen receptor in human osteoblastic cell populations. Calcif Tissue Int 1997; 61:464-473. <<< Important Abstract of Associated reference>>> Kingsmill VJ1, McKay IJ, Ryan P, Ogden MR, Rawlinson SC. Gene expression profiles of mandible reveal features of both calvarial and ulnar bones in the adult rat.J Dent. 2013 Mar;41(3):258-64. doi: 10.1016/j.jdent.2012.11.010. Epub 2012 Nov 23. OBJECTIVES: Limb and mandibular alveolar bone of the mandible are susceptible to disuse osteopenia, whilst skull and mandibular basal bone appear to resist excessive generalised bone loss. We wanted to compare the site-specific transcriptome of anatomically and functionally distinct bones to confirm the composite nature of the mandible at the molecular level. METHODS: Gene expression profiles were obtained for the mandible, ulna, and calvaria of adult male rats using Affymetrix Rat Genome 230 2.0 GeneChips. Ingenuity Pathways Assist generated association maps, and RGD database software identified site-specific pathways. RESULTS: The majority of expressed transcripts (84%) are common to all three sites. The mandible expressed 873 transcripts in common with ulna but not calvaria, and 1014 transcripts in common with calvaria but not ulna. Transcripts in these groups were excluded if they showed significant differential expression (>2-fold) and the remaining mapped genes were filtered for those related to modulation of gene transcription. Analysis of these genes revealed common pathways shared by the mandible and ulna, or mandible and calvaria, which were not shared by the calvaria and ulna. CONCLUSIONS: There were relatively few differences in the expression of genes responsible for the bone formation process per se in different functional skeletal sites. Differential transcription factor expression suggests that it is the regulation of bone formation and not the mechanism of bone formation itself that differs between the skeletal sites. CLINICAL SIGNIFICAN Objectives: The exact genetic difference between the jaw and long bone had not been clearly understood. The purpose of this study was to investigate the difference in gene expression between the human mandible and iliac bone-derived cells. Methods: Primary cells were obtained from mandibular and iliac bone from the 6 healthy, elderly donors (average age 60.2 years) during the reconstruction of mandibular alveolar bone defects. To investigate site-specific difference, within-patient comparison were carried out with cell proliferation and osteoblastic differentiation assay. Gene expression profile of mandible and iliac BC (bone-derived cell) were compared using cDNA microarray analysis using Affymetrix GeneChipM-BM-.. Results: The mandibular BC showed stronger proliferative capacity but weaker osteoblastic differentiation. The comparison of the gene expression profile identified that 82 genes were significantly up-regulated and 66 genes were down-regulated 1.5 fold or greater in mandible compared to iliac BC. The most significantly differentially regulated genes were associated with skeletal system development and morphogenesis (SIX1, MSX1, MSX2, HAND2, PRRX1, OSR2, HOX gene family, PITX2). Microarray analysis revealed that Msx1 was 2.03 fold and Msx2 was 1.99 fold up-regulated in mandible compared to iliac BC (both p<0.01). HOX gene group in mandibular BC was down-regulated (p<0.01). Osteopontin was also 2.84 fold down-regulated in mandible BC (p<0.01). We found that the results of the microarray were reproducible with qRT-PCR. Conclusions: Site-specific difference between jaw and long bone can be explained by the different gene expression pattern, which is primarily related with embryological origin of these two different bones. Human mandible and iliac bone chip was were collected from 6 donors (average 60.2 years, ranged from 56 to 69 years; 3 males, 3 females). Primary cells from this bone chips were utilized to analysis. Therefore 6 sets of iliac and mandibular bone-derived cells were obtained. <<detailed method>> The experimental protocol using human tissue was approved by the Institutional Review Board of Kyungpook National University Hospital (KNUH_10-1093). Informed consent was obtained from each donors who were undergoing iliac bone graft to mandibular alveolar bone defect. To collect osteoblast-like primary cells migrated from bone chips cortical or cortico-cancellous bone was harvested with the similar method described previously. Human mandible and iliac bone chip was were collected from 6 donors (average 60.2 years, ranged from 56 to 69 years; 3 males, 3 females), of healthy general condition without clinical inflammatory lesion in oral cavity. After complete reflection of periosteal layer, the mandibular bone and iliac crest was visualized. Mandibular cortical or cortico-cancellous bone chip was collected by a ronguer during the host bone trimming and decortication procedure for iliac bone graft to edentulous mandible. Similarly, small amount of iliac cortico-cancellous bone chip was collected seperately during the iliac bone harvesting procedure from the same patient. The harvested bone were broke into small pieces and the size of the bone particle became to be 2~4mm in length. The collected bone samples from the two sites were treated with the same method. The bone sample were gently rinsed with Dulbecco's modified Eagle's Medium (DMEM, Lonza Group Ltd., Basel, Switzerland) containing heparin to exclude fat and blood. The particulated bone were then transferred into culture flasks and cultured with DMEM supplemented with 20% fetal bovine serum (FBS, GIBCO-Invetrogen, Carlsbad, CA), 100 U/ml penicillin, 100 mg/ml streptomycin sulphate and 2 mM glutamine incubated at 37M-BM-0C in a humidified atmosphere of 5% CO2 in air. The medium was first changed 2 days after seeding to remove non-adherent cells and the media (DMEM - 20% FBS) was changed every 2 days until the cells migrated out from the explants and reached confluency. Subconfluent primary cells were trypsinized and replated to 75 Cm2 flask. At passage 2, the cells were harvested to extract RNA for cDNA microarray.
2014-06-14 | E-GEOD-58474 | biostudies-arrayexpress
Project description:Mutations within FGFR2 are causative for various craniosynostosis syndromes. The mandibular dysmorphogenesis in these syndromes has rarely been quantitatively characterized prenatally and the cellular and molecular mechanism involved is unclear. To investigate the effects of FGFR2 mutations on development of the mandible, micro-computed tomography (μCT) images were acquired using newborn mice of three Fgfr2-mutant lines associated with Apert and Crouzon craniosynostosis syndromes. Euclidean Distance Matrix Analysis and analysis of relative bone mineral density (BMD) of 3D μCT images revealed differences in mandible morphology and BMD between the mice carrying the Fgfr2 mutations and their unaffected littermates. We further investigated the mechanism for mandibular dysgenesis in the Fgfr2+/S252W (Fgfr2S252W) mouse model that showed the most severe phenotypes. At E16.5, Fgfr2S252W embryos showed an increase in the size of the osteogenic anlagen and Meckel’s cartilage (MC) and altered microarchitecture and mineralization in the mandible relative to unaffected littermates. Laser capture microdissection and RNA-Seq analysis revealed transcriptomic changes in the mandibular bone, highlighting increased expression of genes undergoing osteoclast differentiation and dysregulated genes active in bone mineralization. Increased osteoclastic activity in the mandible of Fgfr2S252W embryos was confirmed and elevated inorganic pyrophosphate concentration was identified due to upregulated expression of Enpp1 and Ank. In contrast, increased proliferation in MC was observed at E12.5. These findings provide evidence that gain-of-function mutations in FGFRs differentially affect intramembranous ossification of dermal bone and cartilage formation contributing to mandibular dysmorphogenesis in craniosynostosis syndromes.
2018-11-07 | GSE121780 | GEO