Unraveling Notch-Dependent Genes in Osteoclast Differentiation: A Novel Approach to Identify Therapeutic Targets for Osteoporosis
Faculty Mentor
Dr. Jason Ashley
Presentation Type
Poster
Start Date
5-8-2024 11:15 AM
End Date
5-8-2024 1:00 PM
Location
PUB NCR
Primary Discipline of Presentation
Biology
Abstract
Within the dynamic process of bone remodeling, osteoclasts play a crucial role in bone resorption, while osteoblasts contribute to bone formation, maintaining skeletal integrity. The equilibrium between these is essential for bone health, as disruptions may lead to conditions like osteoporosis. Osteoclasts originate from macrophages, and their differentiation is regulated, and Notch signaling pathway is a key player in this regulation. Gamma-secretase, an enzyme involved in various cellular functions, regulates the Notch pathway and can be inhibited by DAPT.
Analysis of differentially expressed genes (DEGs) from previous RNASeq experiments conducted on osteoclast differentiation under DAPT treatment identified genes that could potentially be influenced by Notch signaling modulation. However, selecting Notch-specific genes from the broader pool of DEGs poses a challenge due to gamma secretase's involvement in diverse metabolic pathways. To address this, our study employs IMR-1A, an inhibitor disrupting the recruitment of Mastermind-like 1 to the Notch transcriptional activation complex needed to initiate the expression of notch-specific genes.
We categorizes these DEGs into metabolic pathways through gene set enrichment analysis (GSEA). Subsequently, genes will be selected from each pathway, and validation using RT-qPCR will confirm which DEGs are Notch-dependent, shedding light on additional pathways influenced by Notch signaling.
This research aims to differentiate the subset of DEGs influenced by Notch pathway modulation, improving our understanding of its role in cellular processes. Ultimately, identifying key genes involved in Notch signaling may present potential therapeutic targets for mitigating osteoporosis symptoms, such as bone fractures, by inhibiting osteoclast formation.
Recommended Citation
Yu J, Canalis E. Notch and the regulation of osteoclast differentiation and function. Bone. 2020 Sep;138:115474. doi: 10.1016/j.bone.2020.115474. Epub 2020 Jun 8. PMID: 32526405; PMCID: PMC7423683.
Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.
Unraveling Notch-Dependent Genes in Osteoclast Differentiation: A Novel Approach to Identify Therapeutic Targets for Osteoporosis
PUB NCR
Within the dynamic process of bone remodeling, osteoclasts play a crucial role in bone resorption, while osteoblasts contribute to bone formation, maintaining skeletal integrity. The equilibrium between these is essential for bone health, as disruptions may lead to conditions like osteoporosis. Osteoclasts originate from macrophages, and their differentiation is regulated, and Notch signaling pathway is a key player in this regulation. Gamma-secretase, an enzyme involved in various cellular functions, regulates the Notch pathway and can be inhibited by DAPT.
Analysis of differentially expressed genes (DEGs) from previous RNASeq experiments conducted on osteoclast differentiation under DAPT treatment identified genes that could potentially be influenced by Notch signaling modulation. However, selecting Notch-specific genes from the broader pool of DEGs poses a challenge due to gamma secretase's involvement in diverse metabolic pathways. To address this, our study employs IMR-1A, an inhibitor disrupting the recruitment of Mastermind-like 1 to the Notch transcriptional activation complex needed to initiate the expression of notch-specific genes.
We categorizes these DEGs into metabolic pathways through gene set enrichment analysis (GSEA). Subsequently, genes will be selected from each pathway, and validation using RT-qPCR will confirm which DEGs are Notch-dependent, shedding light on additional pathways influenced by Notch signaling.
This research aims to differentiate the subset of DEGs influenced by Notch pathway modulation, improving our understanding of its role in cellular processes. Ultimately, identifying key genes involved in Notch signaling may present potential therapeutic targets for mitigating osteoporosis symptoms, such as bone fractures, by inhibiting osteoclast formation.
