{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T23:15:22Z","timestamp":1792797322756,"version":"4.5.0"},"reference-count":151,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2023,11,17]],"date-time":"2023-11-17T00:00:00Z","timestamp":1700179200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Osteoarthritis (OA) is a complex disease of whole joints with progressive cartilage matrix degradation and chondrocyte transformation. The inflammatory features of OA are reflected in increased synovial levels of IL-1\u03b2, IL-6 and VEGF, higher levels of TLR-4 binding plasma proteins and increased expression of IL-15, IL-18, IL-10 and Cox2, in cartilage. Chondrocytes in OA undergo hypertrophic and senescent transition; in these states, the expression of Sox-9, Acan and Col2a1 is suppressed, whereas the expression of RunX2, HIF-2\u03b1 and MMP-13 is significantly increased. NF-kB, which triggers many pro-inflammatory cytokines, works with BMP, Wnt and HIF-2\u03b1 to link hypertrophy and inflammation. Altered carbohydrate metabolism and the upregulation of GLUT-1 contribute to the formation of end-glycation products that trigger inflammation via the RAGE pathway. In addition, a glycolytic shift, increased rates of oxidative phosphorylation and mitochondrial dysfunction generate reactive oxygen species with deleterious effects. An important surveyor mechanism, the YAP\/TAZ signaling system, controls chondrocyte differentiation, inhibits ageing by protecting the nuclear envelope and suppressing NF-kB, MMP-13 and aggrecanases. The inflammatory microenvironment and synthesis of key matrix components are also controlled by SIRT1 and mTORc. Senescent chondrocytes represent the functional end stage of hypertrophic differentiation and characteristically upregulate p16 and p21, but also a variety of inflammatory cytokines, chemokines and metalloproteinases, developing the senescence-associated secretory phenotype. Senolysis with dendrobin, miR29b-5p and other agents has been shown to be efficient under experimental conditions, and appears to be a promising tool for the treatment of OA, as it restores COL2A1 and aggrecan synthesis, suppressing NF-kB and destructive metalloproteinases.<\/jats:p>","DOI":"10.3390\/ijms242216468","type":"journal-article","created":{"date-parts":[[2023,11,17]],"date-time":"2023-11-17T09:10:38Z","timestamp":1700212238000},"page":"16468","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":103,"title":["Inflammatory and Metabolic Signaling Interfaces of the Hypertrophic and Senescent Chondrocyte Phenotypes Associated with Osteoarthritis"],"prefix":"10.3390","volume":"24","author":[{"given":"Em\u0151ke","family":"Horv\u00e1th","sequence":"first","affiliation":[{"name":"Department of Pathology, Faculty of Medicine, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, 38 Gheorghe Marinescu Street, 540142 Targu Mures, Romania"},{"name":"Pathology Service, County Emergency Clinical Hospital of Targu Mures, 50 Gheorghe Marinescu Street, 540136 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1rp\u00e1d","family":"S\u00f3lyom","sequence":"additional","affiliation":[{"name":"Department of Orthopedics-Traumatology, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, 38 Gh. Marinescu Street, 540142 Targu Mures, Romania"},{"name":"Clinic of Orthopaedics and Traumatology, County Emergency Clinical Hospital of Targu Mures, 50 Gheorghe Marinescu Street, 540136 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e1nos","family":"Sz\u00e9kely","sequence":"additional","affiliation":[{"name":"Clinic of Orthopaedics and Traumatology, County Emergency Clinical Hospital of Targu Mures, 50 Gheorghe Marinescu Street, 540136 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5215-6152","authenticated-orcid":false,"given":"El\u0151d Ern\u0151","family":"Nagy","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Environmental Chemistry, George Emil Palade University of Medicine, Pharmacy, Sciences and Technology of Targu Mures, 38 Gheorghe Marinescu Street, 540142 Targu Mures, Romania"},{"name":"Laboratory of Medical Analysis, Clinical County Hospital Mures, 6 Bern\u00e1dy Gy\u00f6rgy Square, 540394 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hora\u021biu","family":"Popoviciu","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Physical and Medical Rehabilitation, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, 38 Gheorghe Marinescu Street, 540139 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"16044","DOI":"10.1038\/boneres.2016.44","article-title":"Osteoarthritis: Toward a comprehensive understanding of pathological mechanism","volume":"5","author":"Chen","year":"2017","journal-title":"Bone Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1038\/nrrheum.2014.200","article-title":"Origin and function of cartilage stem\/progenitor cells in osteoarthritis","volume":"11","author":"Jiang","year":"2015","journal-title":"Nat. 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