Dataset Information

Alendronate and Osteonecrosis of the Jaw

ABSTRACT: 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.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Osteoblast, Cell Culture

DISEASE(S): Osteonecrosis

SUBMITTER: Sarah Parker

LAB HEAD: jayoung Kim

PROVIDER: PXD024585 | Pride | 2021-09-10

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	200804_DIA_Kim_S1_Repeat.mzML	Mzml
	200804_DIA_Kim_S1_Repeat.raw	Raw
	200804_DIA_Kim_S1_Repeat_out_with_dscore_filtered.csv	Csv
	200804_DIA_Kim_S2_Repeat.mzML	Mzml
	200804_DIA_Kim_S2_Repeat.raw	Raw

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Publications

Alendronate-induced Perturbation of the Bone Proteome and Microenvironmental Pathophysiology.

Kim Jayoung J Yeon Austin A Parker Sarah J SJ Shahid Muhammad M Thiombane Aissatou A Cho Eunho E You Sungyong S Emam Hany H Kim Do-Gyoon DG Kim Minjung M

International journal of medical sciences 20210723 14

<b>Objectives:</b> Bisphosphonates (BPs) are powerful inhibitors of osteoclastogenesis and are used to prevent osteoporotic bone loss and reduce the risk of osteoporotic fracture in patients suffering from postmenopausal osteoporosis. Patients with breast cancer or gynecological malignancies being treated with BPs or those receiving bone-targeted therapy for metastatic prostate cancer are at increased risk of bisphosphonate-related osteonecrosis of the jaw (BRONJ). Although BPs markedly ameliora ...[more]

PMID: 34400895

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