We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Inflammatory and Metabolic Signaling Interfaces of the Hypertrophic and Senescent Chondrocyte Phenotypes Associated with Osteoarthritis.
- Authors
Horváth, Emőke; Sólyom, Árpád; Székely, János; Nagy, Előd Ernő; Popoviciu, Horațiu
- Abstract
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-1β, 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-2α and MMP-13 is significantly increased. NF-kB, which triggers many pro-inflammatory cytokines, works with BMP, Wnt and HIF-2α 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.
- Subjects
BLOOD proteins; RECEPTOR for advanced glycation end products (RAGE); CARRIER proteins; SIRTUINS; NUCLEAR membranes; PHENOTYPES; OSTEOARTHRITIS
- Publication
International Journal of Molecular Sciences, 2023, Vol 24, Issue 22, p16468
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms242216468