Notch signaling is involved in human articular chondrocytes de-differentiation during osteoarthritis
| Autor: | Moncef Hamdoun, Nadia Gadgadi, Slaheddine Sellami, Behrouz Zandieh-Doulabi, Jenneke Klein Nulend, Mohamed Allouche, Nadia Sassi, Slim Mourali, Lilia Laadhar, Sondes Makni |
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| Přispěvatelé: | Oral Cell Biology, Orale Celbiologie (ORM, ACTA) |
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Cartilage
Articular animal structures Cellular differentiation Notch signaling pathway Cell Culture Techniques Osteoarthritis Biochemistry Chondrocytes medicine Basic Helix-Loop-Helix Transcription Factors Humans Molecular Biology Collagen Type II Aggrecan Homeodomain Proteins Metalloproteinase Receptors Notch Chemistry Cartilage Cell Differentiation Cell Biology Dipeptides Cell Dedifferentiation medicine.disease Cell biology Protein Transport medicine.anatomical_structure Immunology Transcription Factor HES-1 Signal transduction Ex vivo Signal Transduction |
| Zdroj: | Sassi, N, Gadgadi, N, Laadhar, L, Allouche, M, Mourali, S, Zandieh-Doulabi, B, Hamdoun, M, Klein Nulend, J, Makni, S & Sellami, S 2014, ' Notch signaling is involved in human articular chondrocytes de-differentiation during osteoarthritis ', Journal of Receptors and Signal Transduction Research, vol. 34, no. 1, pp. 48-57 . https://doi.org/10.3109/10799893.2013.856920 Journal of Receptors and Signal Transduction Research, 34(1), 48-57. Informa Healthcare |
| ISSN: | 1079-9893 |
| DOI: | 10.3109/10799893.2013.856920 |
| Popis: | Context: During osteoarthritis (OA), chondrocytes undergo de-differentiation, resulting in the acquisition of a fibroblast-like morphology, decreased expression of collagen type II (colII) and aggrecan, and increased expression of collagen type I (colI), metalloproteinase 13 (MMP13) and nitric oxide synthase (eNOS). Notch signaling plays a crucial role during embryogenesis. Several studies showed that Notch is expressed in adulthood. Objective: The aim of our study was to confirm the involvement of Notch signaling in human OA at in vitro and ex vivo levels. Materials and methods: Normal human articular chondrocytes were cultured during four passages either treated or not with a Notch inhibitor: DAPT. Human OA cartilage was cultured with DAPT for five days. Chondrocytes secreted markers and some Notch pathway components were analyzed using Western blotting and qPCR. Results: Passaging chondrocytes induced a decrease in the cartilage markers: colII and aggrecan. DAPT-treated chondrocytes and OA cartilage showed a significant increase in healthy cartilage markers. De-differentiation markers, colI, MMP13 and eNOS, were significantly reduced in DAPT-treated chondrocytes and OA cartilage. Notch1 expression was proportional to colI, MMP13 and eNOS expression and inversely proportional to colII and aggrecan expression in nontreated cultured chondrocytes. Notch ligand: Jagged1 increased in chondrocytes culture. DAPT treatment resulted in reduced Jagged1 expression. Notch target gene HES1 increased during chondrocyte culture and was reduced when treated with DAPT. Conclusion: Targeting Notch signaling during OA might lead to the restitution of the typical chondrocyte phenotype and even to chondrocyte redifferentiation during the pathology. |
| Databáze: | OpenAIRE |
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