Identification of Key Genes and Pathways Associated with Sex Differences in Osteoarthritis Based on Bioinformatics Analysis

Wang, Shiying; Wang, Huanmei; Liu, Wei; Wei, Biaofang

doi:10.1155/2019/3482751

Cited by 8 publications

(7 citation statements)

References 43 publications

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“…1 There are multiple factors leading to OA, including traumatic injury, aging, obesity, and other biomechanical disorders. 2,3 The disease is more prevalent in women than in men, and prevalence increases with age, especially after 50 years of age, maybe due to hormonal change. [4][5][6][7] OA of the knee and hand are more prevalent than the OA of hip.…”

Section: Introductionmentioning

confidence: 99%

Women With Osteoarthritis Are at Increased Risk of Ischemic Stroke: A Population-Based Cohort Study

Yeh

Chang²,

Chan³

et al. 2021

Journal of Epidemiology

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Background: Osteoarthritis (OA) is more prevalent in women with age. Comorbidities are prevalent in OA patients. In this study, we conducted a follow-up study to evaluate whether women with OA are at an increased risk of ischemic stroke using insurance claims data of Taiwan. Methods: We identified 13,520 women with OA aged 20-99 newly diagnosed in 2000-2006 and 27,033 women without OA for comparison, frequency matched by age and diagnosis date. Women with baseline history of hypertension and other disorders associated with stroke were excluded for this study. Incident ischemic stroke was assessed by the end of 2013. A nested casecontrol analysis was used to identify factors associated with the stroke in the OA cohort. Results: The incidence rate of ischemic stroke in the OA cohort was 1.5-fold greater than that in comparisons (1.93 versus 1.26 per 1,000 person-years), with an adjusted hazard ratio of 1.34 (95% confidence interval [CI], 1.09-1.66). The nested casecontrol analysis showed that stroke cases were twice as likely to develop hypertension during the follow-up period than controls without stroke. The ischemic stroke risk was significantly associated with hypertension (odds ratio [OR] 1.84; 95% CI, 1.37-2.46) and atrial fibrillation (OR 2.25; 95% CI, 1.24-4.09). Ischemic stroke was not associated with the use of non-steroidal anti-inflammatory drugs or aspirin. Conclusion: Women with OA are at an elevated risk of ischemic stroke. A close monitoring of hypertension, atrial fibrillation, and other stroke related comorbidities is required for stroke prevention for OA patients.

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Section: Introductionmentioning

confidence: 99%

Women With Osteoarthritis Are at Increased Risk of Ischemic Stroke: A Population-Based Cohort Study

Yeh

Chang²,

Chan³

et al. 2021

Journal of Epidemiology

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“…EGF , AQP4 , CDC42 , ERBB2 , and STAT1 have been reported to regulate OA ( 18 , 24 - 26 ), but no such finding has been reported for NTRK3 and CaMK4 . We herein selected EGF , AQP4 , NTRK3 , and CaMK4 for verification.…”

Section: Resultsmentioning

confidence: 96%

Identification of CaMK4 as a sex-difference-related gene in knee osteoarthritis

Feng¹,

Zhang²,

Li³

et al. 2023

Ann Transl Med

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Background: Osteoarthritis (OA) is a common degenerative joint disease with a higher prevalence in females than in males. Sex may be a key factor affecting the progression of OA. This study aimed to investigate critical sex-difference-related genes in patients with OA and confirm their potential roles in OA regulation.Methods: OA datasets GSE12021, GSE55457, and GSE36700 were downloaded from the Gene Expression Omnibus database to screen OA-causing genes that are differentially expressed in the two sexes.Cytoscape was used to construct a protein-protein interaction network and determine hub genes. Synovial tissues of patients (male and female) with OA and female non-OA healthy controls were obtained to confirm the expression of hub genes and screen the key genes among them. Destabilization of the medial meniscus (DMM)-induced OA mice model was established to verify the screened key genes. Hematoxylin and eosin (HE) staining and Safranin O-fast green dye staining were employed to observe synovial inflammation and pathological cartilage status.Results: The abovementioned three datasets were intersected to obtain 99 overlapping differentially expressed genes, of which 77 were upregulated and 22 were downregulated in female patients with OA.The hub genes screened were EGF, AQP4, CDC42, NTRK3, ERBB2, STAT1, and CaMK4. Among them, Ca 2+ /calmodulin-dependent protein kinase-4 (CaMK4) was identified as a key sex-related gene for OA. It was significantly higher in female OA patients than in the cases of male patients. Moreover, CaMK4 was significantly increased in female patients with OA compared with the female non-OA group. These results suggest that CaMK4 plays an important role in the progression of OA. OA mouse models demonstrated that CaMK4 expression in the mice knee joint synovial tissue elevated after DMM, with aggravated synovial inflammation and significant cartilage damage. Cartilage damage improved after intraperitoneal administration of the CaMK4 inhibitor KN-93.Conclusions: CaMK4 is a key sex-related gene influencing the progression and pathogenesis of OA and may be considered as a new target for OA treatment.

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“…There are no precise methods to identify hub genes. Some researchers select the higher-degree nodes in the PPI network as hub genes, 61 while others identify the hub genes via cytoHubba in Cytoscape using a single method. 62 In addition, some researchers believe that the overlapping results from several methods in cytoHubba is a more reasonable method for detecting hub genes.…”

Section: Discussionmentioning

confidence: 99%

<p>Identification of Key Genes Associated with Changes in the Host Response to Severe Burn Shock: A Bioinformatics Analysis with Data from the Gene Expression Omnibus (GEO) Database</p>

Xiao¹,

Duan²,

Gong³

et al. 2020

JIR

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Background: Patients with severe burns continue to display a high mortality rate during the initial shock period. The precise molecular mechanism underlying the change in host response during severe burn shock remains unknown. This study aimed to identify key genes leading to the change in host response during burn shock. Methods: The GSE77791 dataset, which was utilized in a previous study that compared hydrocortisone administration to placebo (NaCl 0.9%) in the inflammatory reaction of severe burn shock, was downloaded from the Gene Expression Omnibus (GEO) database and analyzed to identify the differentially expressed genes (DEGs). Functional enrichment analyses of Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were performed. The protein-protein interaction (PPI) network of DEGs was constructed using the Search Tool for the Retrieval of Interacting Genes (STRING) database and then visualized in Cytoscape. In addition, important modules in this network were selected using the Molecular Complex Detection (MCODE) algorithm, and hub genes were identified in cytoHubba, a Cytoscape plugin. Results: A total of 1059 DEGs (508 downregulated genes and 551 upregulated genes) were identified from the dataset. The DEGs enriched in GO terms and KEGG pathways were related to immune response. The PPI network contained 439 nodes and 2430 protein pairs. Finally, important modules and hub genes were identified using the different Cytoscape plugins. The key genes in burn shock were identified as arginase 1 (ARG1), cytoskeleton-associated protein (CKAP4), complement C3a receptor (C3AR1), neutrophil elastase (ELANE), gamma-glutamyl hydrolase (GGH), orosomucoid (ORM1), and quiescin sulfhydryl (QSOX1). Conclusion: The DEGs, functional terms and pathways, and hub genes identified in the present study can help shed light on the molecular mechanism underlying the changes in host response during burn shock and provide potential targets for early detection and treatment of burn shock.

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Identification of Key Genes and Pathways Associated with Sex Differences in Osteoarthritis Based on Bioinformatics Analysis

Cited by 8 publications

References 43 publications

Women With Osteoarthritis Are at Increased Risk of Ischemic Stroke: A Population-Based Cohort Study

Women With Osteoarthritis Are at Increased Risk of Ischemic Stroke: A Population-Based Cohort Study

Identification of CaMK4 as a sex-difference-related gene in knee osteoarthritis

<p>Identification of Key Genes Associated with Changes in the Host Response to Severe Burn Shock: A Bioinformatics Analysis with Data from the Gene Expression Omnibus (GEO) Database</p>

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