Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1221230 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR32277400_1.fastq.gz | Fastqsanger.gz | |||
| SRR32277400_2.fastq.gz | Fastqsanger.gz | |||
| SRR32277401_1.fastq.gz | Fastqsanger.gz | |||
| SRR32277401_2.fastq.gz | Fastqsanger.gz | |||
| SRR32277402_1.fastq.gz | Fastqsanger.gz |
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Project description:Genome sequencing of Actinomyces from medication-related osteonecrosis of the jaw (MRONJ)
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Project description:Detached osteoclasts in the granulation tissue surrounding sequestra in medication-related osteonecrosis of the jaw
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Project description:BACKGROUND:; Osteonecrosis of the jaw (ONJ) has been reported in patients with a history of aminobisphosphonate use. METHODS:; In order to define ONJ and gain insights into its pathophysiology, clinical, radiographic, biochemical, and microarray profiling studies were conducted in 11 patients with multiple myeloma (MM) and ONJ. RESULTS:; Eleven patients between the ages of 57 and 81 yrs were treated with either pamidronate (n=3), zoledronate (n=4), or both agents sequentially (n=4) for a mean of 38.7 months. Radiographic studies demonstrated radiolucency and sclerosis on plain films. Functional imaging with positron emission tomography (PET) demonstrated a visual increase in glucose metabolism and mineralization at sites of ONJ, using fluorodeoxyglucose (FDG) and sodium fluoride (NaF), respectively. Quantitative regional analysis confirmed an increased standardized uptake value (SUVmax) in areas of ONJ. The target to background ratio of SUVmax was significantly greater for NaF-PET than FDG-PET scans, suggesting that NaF-PET may provide superior image quality for identifying ONJ. Transcriptional profiling of peripheral blood mononuclear cells (PBMCs) using the Affymetrix U133Plus 2.0 gene chip in all 11 MM patients compared with 10 age matched MM controls and 5 healthy volunteers demonstrated that genes involved in osteoblast and osteoclast signaling cascades were significantly downregulated in patients with ONJ, as were proteins confirmed by ELISA. CONCLUSIONS:; ONJ is seen in patients with a history of aminobisphosphonate use. Functional imaging with NaF PET confirms the diagnosis of ONJ. Gene and protein studies are consistent with altered bone remodeling, evidenced by suppression of both bone resorption and formation. Experiment Overall Design: Transcriptional profiling of peripheral blood mononuclear cells (PBMCs) was performed using the Affymetrix U133Plus 2.0 Gene Chip (Affymetrix, Santa Clara, CA, USA) in 11 patients with osteonecrosis of the jaw and multiple myeloma and compared with the profiles of the 10 myeloma patients on bisphosphonate therapy without osteonecrosis of the jaw and 5 healthy volunteers.
2008-06-15 | E-GEOD-7116 | biostudies-arrayexpress
Project description:Purpose: The goal of this study was to characterize the gingival oral barrier immunity of bisphosphonate-related osteonecrosis of the jaw (BRONJ) and HMDP-treated BRONJ mouse maxilla. Method: Mouse BRONJ was induced by Zoledronate IV injection and maxillary left first molar extraction. HMDP-DNV was topically applied to the BRONJ lesion 2 times. Mouse palatal gingiva was harvested 2 weeks after tooth extraction. Gingival cells were harvested and subjected to 10X Genomix scRNA-seq. Cell Ranger processed data were analysed.
2022-01-08 | GSE193110 | GEO
Project description:Medication-related osteonecrosis of the jaw (MRONJ) is a rare but serious complication of anti-resorptive agents used for osteoporosis and bone metastasis. As the global population ages, the number of patients with MRONJ continues to rise. Resorptive osteoclasts firmly attached to bone surfaces cannot be detected using single-cell RNA-Seq (scRNA-Seq); however, we hypothesized that multinucleated giant and detached osteoclasts (DetOCs) can be detected by this method. scRNA-Seq was performed on granulation tissues surrounding sequestra from four patients with MRONJ and radicular cysts, a common odontogenic infectious disease with normal bone metabolism. Our results show that DetOCs were detected exclusively in the granulation tissues of MRONJ. These DetOCs expressed well-known osteoclast markers as well as COL27A1. Subcluster analysis revealed that SPP1+ TREM2+ macrophages differentiated into DetOCs and expressed several types of collagens. Immunostaining confirmed the expression of COL27A1 in DetOCs in MRONJ, as well as in osteoclasts in mandibular cancer. Overall, we successfully identified DetOCs in the granulation tissues surrounding sequestra in MRONJ, and our scRNA-Seq analysis suggests the potential to classify osteoclast subtypes based on the expression of collagen types.
2025-11-27 | GSE303003 | GEO
Project description:Oral microbiome in patients with osteonecrosis of the jaw
| PRJDB14257 | ENA
Project description:Mitochondria-driven macrophage dysregulation plays a crucial role in the progression of various inflammatory diseases, yet its exact mechanism in the pathogenesis of bisphosphonate-related osteonecrosis of the jaw (BRONJ) remains poorly understood. Here, we demonstrate that zoledronic acid (ZA) impairs mitochondrial bioenergetic function in macrophages, resulting in elevated mitochondrial membrane potential, accumulated mitochondrial reactive oxygen species, and increased expression of HIF-1α, which subsequently promotes a pro-inflammatory transition in macrophages. Importantly, ZA inhibits autophagy-initiating complex via activation of the TLR4-MyD88/PI3K-AKT-mTOR pathway, thereby impeding clearance of dysfunctional mitochondria to sustain superoxide production.
2026-03-04 | GSE306512 | GEO
Project description:The nitrogen containing bisphosphonates (NBP), pamidronate, is considered to be responsible for Medication Related Osteonecrosis of the Jaw, MRONJ. By inhibiting the prenylation of G-proteins necessary for osteoclast survival, the NBP blocks the synthesis of geranylgeraniol(GGOH) in the mevalonic acid pathway.The goal of the study is to assess the effect of pamidronate on global gene expression and determine whether administration of GGOH can restore gene expression. RAW osteoclast-like cells were maintained in monolayer culture and treated with RANKL in the presence and absence of NBP.Pamidronate-treated cells were also treated with GGOH to restore normal function. RNA was extracted from pelleted RANKL-treated cells, sequenced and pathway analyzed. Pamidronate downregulated genes associated with immune function, oxidative metabolism and osteoclast differentiation and function.Surprisingly, Rho j, a small GTPase was down-regulated 238 fold while RGS18 protein, a regulator of G-protein signaling, was repressed 126 fold. Substantial changes in expression of more than twenty other G-proteins were observed.When cells were treated with GGOH, many of the inhibitory effects of the NBP were abrogated and G-protein expression was preserved. The observation that GGOH overcomes the deleterious effect of NBP on osteoclasts by promoting G-protein expression, suggests a novel therapeutic approach to preventing or treating MRONJ.
2026-04-30 | GSE296096 | GEO
Project description:Bisphosphonate related osteonecrosis of the jaw is associated with polymorphisms of the cytochrome P450 CYP2C8 in MM
| PRJNA105805 | ENA
Project description:This dataset contains data-independent acquisition (DIA) LC–MS/MS proteomic profiles of human mandible tissues obtained from patients with bisphosphonate-related osteonecrosis of the jaw (BRONJ) and healthy controls. Frozen tissues were processed using phenol–methanol extraction, SP3-based cleanup, and tryptic digestion, followed by high-resolution LC–MS/MS in DIA mode. Protein identification and quantification were performed under a 1% FDR cutoff with intensity-based normalization. Comparative analysis revealed key alterations in BRONJ samples.
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