Meta-analysis and multi-omics to elucidate pathogenic mechanisms of age-related knee osteoarthritis
Meta-analysis and multi-omics to elucidate pathogenic mechanisms of age-related knee osteoarthritis
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 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.
Ambrosio Fabrisia、Gilmer Gabrielle、Wang Kai、Sivakumar Sruthi、Matsui Yusuke、Evans Christopher、Iijima Hirotaka
Department of Physical Medicine and Rehabilitation, University of Pittsburgh||McGowan Institute for Regenerative Medicine, University of Pittsburgh||Department of Bioengineering, University of Pittsburgh, Pittsburgh||Department of Environmental and Occupational Health, University of PittsburghMedical Scientist Training Program, School of Medicine, University of Pittsburgh||Department of Bioengineering, University of Pittsburgh, PittsburghDepartment of Physical Medicine and Rehabilitation, University of Pittsburgh||McGowan Institute for Regenerative Medicine, University of PittsburghDepartment of Physical Medicine and Rehabilitation, University of Pittsburgh||Department of Bioengineering, University of Pittsburgh, PittsburghBiomedical and Health Informatics Unit, Graduate School of Medicine, Nagoya UniversityRehabilitation Medicine Research Center, Mayo ClinicDepartment of Physical Medicine and Rehabilitation, University of Pittsburgh||McGowan Institute for Regenerative Medicine, University of Pittsburgh||Japan Society for the Promotion of Science
医学研究方法基础医学分子生物学
Articular cartilageAgingMeta-analysisBioinformaticsAGE-RAGE signaling pathway
Ambrosio Fabrisia,Gilmer Gabrielle,Wang Kai,Sivakumar Sruthi,Matsui Yusuke,Evans Christopher,Iijima Hirotaka.Meta-analysis and multi-omics to elucidate pathogenic mechanisms of age-related knee osteoarthritis[EB/OL].(2025-03-28)[2025-07-02].https://www.biorxiv.org/content/10.1101/2021.05.06.442993.点此复制
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