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Current Bioinformatics


ISSN (Print): 1574-8936
ISSN (Online): 2212-392X

Research Article

Identification of Critical Functional Modules and Signaling Pathways in Osteoporosis

Author(s): Xiaowei Jiang*, Pu Ying*, Yingchao Shen, Yiming Miu, Wenbin Kong, Tong Lu and Qiang Wang

Volume 16, Issue 1, 2021

Published on: 05 July, 2020

Page: [90 - 97] Pages: 8

DOI: 10.2174/1574893615999200706002411

Price: $65


Background: Osteoporosis is the most common bone metabolic disease. Abnormal osteoclast formation and resorption play a fundamental role in osteoporosis pathogenesis. Recent researches have greatly broadened our understanding of molecular mechanisms of osteoporosis. However, the molecular mechanisms leading to osteoporosis are still not entirely clear.

Objective: The purpose of this work is to study the critical regulatory genes, functional modules, and signaling pathways.

Methods: Differential expression analysis, network topology-based analysis, and overrepresentation enrichment analysis (ORA) were used to identify differentially expressed genes (DEGs), gene subnetworks, and signaling pathways related to osteoporosis, respectively.

Results: Differential expression analysis identified DEGs, such as POGLUT1, DAPK3 and NFKBIA, associated with osteoclastogenesis, which highlighted Notch, apoptosis and NF-kB signaling pathways. Network topology-based analysis identified the upregulated subnetwork characterized by EXOSC8 and DIS3L from the RNA exosome complex, and the downregulated subnetwork composed of histone deacetylases and the cofactors, MORF4L1 and JDP2. Furthermore, the overrepresentation enrichment analysis highlighted that corticotrophin-releasing hormone signaling pathway might affect osteoclastogenesis through its component NR4A1, and suppressing osteoclast differentiation and osteoclast bone resorption with urocortin (UCN).

Conclusion: Our systematic analysis not only discovered novel molecular mechanisms but also proposed potential drug targets for osteoporosis.

Keywords: Osteoporosis, critical regulatory genes, functional modules, signaling pathways, osteoclastogenesis, hormone.

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