PMID- 34348542 OWN - NLM STAT- MEDLINE DCOM- 20220202 LR - 20220202 IS - 1744-8387 (Electronic) IS - 1478-9450 (Linking) VI - 18 IP - 7 DP - 2021 Jul TI - Chondrocyte protein co-synthesis network analysis links ECM mechanosensing to metabolic adaptation in osteoarthritis. PG - 623-635 LID - 10.1080/14789450.2021.1962299 [doi] AB - BACKGROUND: Knee osteoarthritis (OA) is one of the most common structural OA disorders globally. Incomplete understanding of the fundamental biological aspects of osteoarthritis underlies the current lack of effective treatment or disease modifying drugs. RESEARCH DESIGN AND METHODS: We implemented a systems approach by making use of the statistical network concepts in Weighted Gene Co-expression Analysis to reconstruct the organization of the core proteome network in chondrocytes obtained from OA patients and healthy individuals. Protein modules reflect groups of tightly co-ordinated changes in protein abundance across healthy and OA chondrocytes. RESULTS: The unbiased systems analysis identified extracellular matrix (ECM) mechanosensing and glycolysis as two modules that are most highly correlated with OmicronAlpha. The ECM module was enriched in the OA genetic risk factors tenascin-C (TNC) and collagen 11A1 (COL11A1), as well as in cartilage oligomeric matrix protein (COMP), a biomarker associated with cartilage integrity. Mapping proteins that are unique to OA or healthy chondrocytes onto the core interactome, which connects microenvironment sensing and regulation of glycolysis, identified differences in metabolic and anti-inflammatory adaptation. CONCLUSION: The interconnection between cartilage ECM remodeling and metabolism is indicative of the dynamic chondrocyte states and their significance in osteoarthritis. FAU - Destouni, Aspasia AU - Destouni A AD - Laboratory of Cytogenetics and Molecular Genetics, Faculty of Medicine, University of Thessaly, Larissa, Greece. FAU - Tsolis, Konstantinos C AU - Tsolis KC AD - KULeuven, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Laboratory of Molecular Bacteriology, Leuven, Belgium. FAU - Economou, Anastassios AU - Economou A AD - KULeuven, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Laboratory of Molecular Bacteriology, Leuven, Belgium. FAU - Papathanasiou, Ioanna AU - Papathanasiou I AD - Laboratory of Cytogenetics and Molecular Genetics, Faculty of Medicine, University of Thessaly, Larissa, Greece. AD - Department of Biology, Faculty of Medicine, University of Thessaly, Larissa, Greece. FAU - Balis, Charalampos AU - Balis C AD - Laboratory of Cytogenetics and Molecular Genetics, Faculty of Medicine, University of Thessaly, Larissa, Greece. FAU - Mourmoura, Evanthia AU - Mourmoura E AD - Laboratory of Cytogenetics and Molecular Genetics, Faculty of Medicine, University of Thessaly, Larissa, Greece. FAU - Tsezou, Aspasia AU - Tsezou A AD - Laboratory of Cytogenetics and Molecular Genetics, Faculty of Medicine, University of Thessaly, Larissa, Greece. AD - Department of Biology, Faculty of Medicine, University of Thessaly, Larissa, Greece. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210811 PL - England TA - Expert Rev Proteomics JT - Expert review of proteomics JID - 101223548 SB - IM MH - Cells, Cultured MH - *Chondrocytes MH - Extracellular Matrix MH - Humans MH - *Osteoarthritis OTO - NOTNLM OT - Chondrocyte proteome OT - mechanosensing OT - mechanotransduction OT - microenvironment OT - osteoarthritis OT - protein co-synthesis network analysis EDAT- 2021/08/06 06:00 MHDA- 2022/02/03 06:00 CRDT- 2021/08/05 05:27 PHST- 2021/08/06 06:00 [pubmed] PHST- 2022/02/03 06:00 [medline] PHST- 2021/08/05 05:27 [entrez] AID - 10.1080/14789450.2021.1962299 [doi] PST - ppublish SO - Expert Rev Proteomics. 2021 Jul;18(7):623-635. doi: 10.1080/14789450.2021.1962299. Epub 2021 Aug 11.