Identification of drug candidate for osteoporosis by computational bioinformatics analysis of gene expression profile

Abstract

BackgroundOsteoporosis is a condition of bones that leads to an increased susceptibility to fracture and consequent painful morbidity. It has become a major issue of life quality worldwide. However, until now, the molecular mechanism of this disease is far from being clear.MethodsIn this study, we obtained the gene expression profile of osteoporosis and controls from Gene Expression Omnibus and identified differentially expressed genes (DEGs) using classical t-test method. Then, functional enrichment analyses were performed to identify the dysregulated Gene Ontology categories and dysfunctional pathways in osteoporosis patients compared to controls. Besides, the connectivity map was used to identify compounds that induced inverse gene changes to osteoporosis.ResultsA total of 5581 DEGs were identified. We found these DEGs were enriched in 9 pathways by pathway enrichment analysis, including focal adhesion and MAPK signaling pathway. Besides, sanguinarine was identified as a potential therapeutic drug candidate capable of targeting osteoporosis.ConclusionAlthough candidate agents identified by our approach may be premature for clinical trials, it is clearly a direction that warrants additional consideration.

Bioinformatics Accelerates the Major Tetrad: A Real Boost for the Pharmaceutical Industry

“…The genetic expression profiles in osteoporosis were developed from information in Gene Expression Omnibus, in an investigation associated with osteoporosis-related drug targets [41]. A classical t-test method has been employed for the analysis of differentially expressed genes (DEGs).…”

Characterization of Dysregulated lncRNA-Associated ceRNA Network Reveals Novel lncRNAs With ceRNA Activity as Epigenetic Diagnostic Biomarkers for Osteoporosis Risk

“…Traditional markers for osteoporosis risk are BMD, vitamin D, alkaline phosphatase, and so on (Parveen et al, 2019). Increasing evidence has suggested that altered molecular profiles contributed to the osteoporosis and outcome, which provided novel insights into molecular basis of osteoporosis and also highlighted the potential of molecular factors as markers for osteoporosis diagnosis and prognosis (Yu et al, 2013;Makitie et al, 2018;Gong et al, 2019;Ukon et al, 2019). Biomarker identification has been proven to be an effective way to recognize people at high risk for developing osteoporosis and have attracted much attention in the clinical decision-making for osteoporosis management.…”

Anti‐osteoporosis activity of Sanguinarine in preosteoblast MC3T3‐E1 cells and an ovariectomized rat model

“…It is well‐known that unbalance bone remodeling plays a key role in osteoporosis pathogenesis (Kling et al, ). Sanguinarine was identified as a potential drug candidate for osteoporosis treatment in a computational bioinformatics study (Yu et al, ). Li et al () found that Sanguinarine could suppress osteoclastic bone resorption and osteoclast formation in vitro.…”

“…AMPK (Jang, Kim, Lee, Son, & Koh, ) and BMP2 (Takuwa et al, ) can activate the phosphorylation of Smad1/5/8, thus stimulating ALP activity in osteoblastic MC3T3‐E1 cells. By computational bioinformatics analysis, Yu, Wang, Li, Ma, and Li () identified Sanguinarine (13‐methyl [1,3] benzodioxolo [5,6‐c]‐1,3‐dioxolo [4,5] phenanthridinium) as a potential drug candidate for osteoporosis treatment. Sanguinarine, derived from the root of Sanguinaria canadendid and other poppyfumaria species, has been demonstrated to exert antimicrobial (Godowski, ), anti‐inflammatory (Niu, Fan, Li, Xing, & Huang, ), and anti‐tumor activities (Adhami et al, ; Ahmad, Gupta, Husain, Heiskanen, & Mukhtar, ; Pica et al, ; Sun et al, ).…”