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Single Cell RNA sequencing of BRONJ disease control and HMDP-treated mouse gingiva

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE193110 | GEO | 2022/01/08

REPOSITORIES: GEO

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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.

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Single Cell RNA sequencing of BRONJ disease control and HMDP-treated mouse gingiva

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