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Meta-analysis and multi-omics to elucidate pathogenic mechanisms of age-related knee osteoarthritis
by
Gilmer, Gabrielle
, Ambrosio, Fabrisia
, Evans, Christopher
, Iijima, Hirotaka
, Sivakumar, Sruthi
, Matsui, Yusuke
, Wang, Kai
in
Molecular Biology
2021
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Meta-analysis and multi-omics to elucidate pathogenic mechanisms of age-related knee osteoarthritis
by
Gilmer, Gabrielle
, Ambrosio, Fabrisia
, Evans, Christopher
, Iijima, Hirotaka
, Sivakumar, Sruthi
, Matsui, Yusuke
, Wang, Kai
in
Molecular Biology
2021
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Meta-analysis and multi-omics to elucidate pathogenic mechanisms of age-related knee osteoarthritis
Paper
Meta-analysis and multi-omics to elucidate pathogenic mechanisms of age-related knee osteoarthritis
2021
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Overview
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.
Publisher
Cold Spring Harbor Laboratory
Subject
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