Integrated approach of meta-analysis and bioinformatics towards elucidating disease mechanisms associated with age-related knee osteoarthritis

2021 ◽  
Vol 29 ◽  
pp. S16
Author(s):  
H. Iijima ◽  
G. Gilmer ◽  
K. Wang ◽  
S. Sivakumar ◽  
Y. Matsui ◽  
...  
Keyword(s):  
Knee Osteoarthritis ◽  
Meta Analysis ◽  
Integrated Approach ◽  
Disease Mechanisms ◽  
Age Related

scholarly journals Meta-analysis and multi-omics to elucidate pathogenic mechanisms of age-related knee osteoarthritis

2021 ◽  
Author(s):  
Hirotaka Iijima ◽  
Gabrielle Gilmer ◽  
Kai Wang ◽  
Sruthi Sivakumar ◽  
Christopher Evans ◽  
...  
Keyword(s):  
Knee Osteoarthritis ◽  
Meta Analysis ◽  
Great Majority ◽  
Integrated Approach ◽  
Pathogenic Mechanisms ◽  
Age Related ◽  
Level Data ◽  
Model Protein ◽  
Post Traumatic ◽  
Surgically Induced

Increased mechanistic insight into the pathogenesis of knee osteoarthritis (KOA) is needed to develop efficacious disease-modifying treatments. Though age-related pathogenic mechanisms are most relevant to the great majority of KOA seen clinically, the bulk of our mechanistic understanding of KOA has been derived using surgically induced post-traumatic OA (PTOA) models. Here, we took an integrated approach of meta-analysis and multi-omics to elucidate pathogenic mechanisms of age-related KOA in murine model. Protein-level data together with transcriptomic profiling revealed inflammation, autophagy, and cellular senescence as primary hallmarks of age-related KOA. Importantly, the molecular profiles of aged cartilage were unique from those in PTOA, with only 1% overlap between the two. At the nexus of aging hallmarks, Advanced Glycation End-Product (AGE)/Receptor for AGE emerged as intrinsically linked to age-related KOA. This pathway was further validated by mass spectrometry. Collectively, these findings implicate dysregulation of AGE-RAGE signaling as a key driver of age-related KOA.

Meta-analysis integrated with multi-omics data analysis to elucidate pathogenic mechanisms of age-related knee osteoarthritis in mice

2022 ◽  
Author(s):  
Hirotaka Iijima ◽  
Gabrielle Gilmer ◽  
Kai Wang ◽  
Sruthi Sivakumar ◽  
Christopher Evans ◽  
...  
Keyword(s):  
Data Analysis ◽  
Knee Osteoarthritis ◽  
Meta Analysis ◽  
Integrated Approach ◽  
Mass Spectrometry Data ◽  
Omics Data ◽  
Pathogenic Mechanisms ◽  
Age Related ◽  
Level Data ◽  
Omics Data Analysis

Abstract Increased mechanistic insight into the pathogenesis of knee osteoarthritis (KOA) is needed to develop efficacious disease-modifying treatments. Though age-related pathogenic mechanisms are most relevant to the majority of clinically-presenting KOA, the bulk of our mechanistic understanding of KOA has been derived using surgically induced post-traumatic OA (PTOA) models. Here, we took an integrated approach of meta-analysis and multi-omics data analysis to elucidate pathogenic mechanisms of age-related KOA in mice. Protein-level data were integrated with transcriptomic profiling to reveal inflammation, autophagy, and cellular senescence as primary hallmarks of age-related KOA. Importantly, the molecular profiles of cartilage aging were unique from those observed following PTOA, with less than 3% overlap between the two models. At the nexus of the three aging hallmarks, Advanced Glycation End-Product (AGE)/Receptor for AGE emerged as the most statistically robust pathway associated with age-related KOA. This pathway was further supported by analysis of mass spectrometry data. Notably, the change in AGE-RAGE signaling over time was exclusively observed in male mice, suggesting sexual dimorphism in the pathogenesis of age-induced KOA in murine models. Collectively, these findings implicate dysregulation of AGE-RAGE signaling as a sex-dependent driver of age-related KOA.

scholarly journals Comparative efficacy and safety of different regimens of ranibizumab for neovascular age-related macular degeneration: a network meta-analysis of randomised controlled trials

BMJ Open ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. e040906
Author(s):  
Xinyu Zhao ◽  
Lihui Meng ◽  
Youxin Chen
Keyword(s):  
Adverse Events ◽  
Macular Degeneration ◽  
Randomised Controlled Trials ◽  
Meta Analysis ◽  
Age Related Macular Degeneration ◽  
Controlled Trials ◽  
Cochrane Central Register ◽  
Efficacy And Safety ◽  
Age Related ◽  
Randomised Controlled

ObjectiveTo give a comprehensive efficacy and safety ranking of different therapeutic regimens of ranibizumab for neovascular age-related macular degeneration (nAMD).DesignA systematic review and network meta-analysis.MethodsThe PubMed, Embase, Cochrane Central Register of Controlled Trials, and other clinical trial registries were searched up to 1 October 2019 to identify related randomised controlled trials (RCT) of different regimens of ranibizumab for nAMD. The primary efficacy outcome was the changes of best-corrected visual acuity (BCVA) at 1 year, the primary safety outcome was the incidence of severe ocular adverse events. Secondary outcomes such as changes of central retinal thickness (CRT) were evaluated. We estimated the standardised mean difference (SMD), ORs, 95% CIs, the surface under the cumulative ranking curves and the mean ranks for each outcome using network meta-analyses with random effects by Stata 14.0.ResultsWe identified 26 RCTs involving 10 821 patients with nAMD randomly assigned to 21 different therapeutic regimens of ranibizumab or sham treatment. Ranibizumab 0.5 mg (treat and extend, T&E) is most effective in terms of changes of BCVA (letters, SMD=21.41, 95% CI 19.86 to 22.95) and three or more lines of BCVA improvement (OR=2.83, 95% CI 1.27 to 4.38). However, it could not significantly reduce retreatment times compared with monthly injection (SMD=−0.94, 95% CI −2.26 to 0.39). Ranibizumab 0.5 mg (3+pro re nata)+non-steroidal anti-inflammatory drugs (NSAIDs) is most effective in reducing CRT and port delivery system of ranibizumab (100 mg/mL) could reduce the number of retreatment most significantly. All regimes have no more risk of severe ocular complications (including vitreous haemorrhage, rhegmatogenous retinal detachment, endophthalmitis, retinal tear and retinal pigment epithelium tear) or cardiocerebral vascular complications.ConclusionsRanibizumab 0.5 mg (T&E) is most effective in improving the visual outcome. The administration of topical NSAIDs could achieve additional efficacy in CRT reduction and visual improvement. Both interventions had acceptable risks of adverse events.

Association between hip and knee osteoarthritis with falls: a systematic review and meta‐analysis

2021 ◽  
Author(s):  
Zhen‐han Deng ◽  
Jian Xu ◽  
Lu‐jue Long ◽  
Fei Chen ◽  
Kang Chen ◽  
...  
Keyword(s):  
Systematic Review ◽  
Knee Osteoarthritis ◽  
Meta Analysis
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