Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8257207 | Ageing Research Reviews | 2018 | 16 Pages |
Abstract
Ageing processes play a major contributing role for the development of Osteoarthritis (OA). This prototypic degenerative condition of ageing is the most common form of arthritis and is accompanied by a general decline, chronic pain and mobility deficits. The disease is primarily characterized by articular cartilage degradation, followed by subchondral bone thickening, osteophyte formation, synovial inflammation and joint degeneration. In the early stages, osteoarthritic chondrocytes undergo phenotypic changes that increase cell proliferation and cluster formation and enhance the production of matrix-remodelling enzymes. In fact, chondrocytes exhibit differentiation plasticity and undergo phenotypic changes during the healing process. Current studies are focusing on unravelling whether OA is a consequence of an abnormal wound healing response. Recent investigations suggest that alterations in different proteins, such as TGF-Ã/BMPs, NF-KÃ, Wnt, and Cx43, or SASP factors involved in signalling pathways in wound healing response, could be directly implicated in the initiation of OA. Several findings suggest that osteoarthritic chondrocytes remain in an immature state expressing stemness-associated cell surface markers. In fact, the efficacy of new disease-modifying OA drugs that promote chondrogenic differentiation in animal models indicates that this may be a drug-sensible state. In this review, we highlight the current knowledge regarding cellular plasticity in chondrocytes and OA. A better comprehension of the mechanisms involved in these processes may enable us to understand the molecular pathways that promote abnormal repair and cartilage degradation in OA. This understanding would be advantageous in identifying novel targets and designing therapies to promote effective cartilage repair and successful joint ageing by preventing functional limitations and disability.
Keywords
Oct4OP-1CTDGJICGDF5SCIDCCAAT/enhancer binding protein betaPARPWntconnexinsECMTGF-ßVCAMConnexin43GAGssevere combined immune deficientSASPZIP8FLNAGrowth and Differentiation Factor 5mRNATNFαCX43KartogeninSRY-related HMG boxMmpsMSCsBMPsC/EBPsMAPKmessenger RNARNA interferenceRNAiROSsIL-6RSOxArthritisRheumatoid arthritisALPAlkaline phosphataseoleuropein aglyconeGap junction intercellular communicationOsteoarthritisWound Healingepithelial to mesenchymal transitioninterleukinsenescence-associated beta-galactosidasetransforming growth factor-betaCxstumour necrosis factor alphaEMTC-terminal domainFilamin AAgeingwingless-related integration siteES cellsMesenchymal stem cellsEmbryonic stem cellsCIAnuclear factor of activated T-cellsCartilageoctamer-binding transcription factor 4nuclear factor kappa-light-chain-enhancer of activated B cellsSenescence-associated secretory phenotypeExtracellular matrixfibroblast-like synoviocytesMatrix metalloproteinasesmesenchymal to epithelial transitionMETNitric oxideOsteogenic protein-1bone morphogenetic proteinsVascular cell adhesion protein-1mitogen-activated protein kinasepoly ADP ribose polymeraseSenescencearticular chondrocyteGlycosaminoglycansReactive oxygen species
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Ageing
Authors
Marta Varela-Eirin, Jesus Loureiro, Eduardo Fonseca, Silvia Corrochano, Jose R. Caeiro, Manuel Collado, Maria D. Mayan,