Type II TGFβ receptor modulates chondrocyte phenotype
| Autor: | Elise Duval, Sylvain Leclercq, Catherine Baugé, Philippe Galéra, Nicolas Girard, Karim Boumediene, David Ollitrault |
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| Přispěvatelé: | Normandie Université ( NU ), Microenvironnement cellulaire et pathologie ( MILPAT ), Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Département de chirurgie orthopédique, Clinique Saint Martin, Normandie Université (NU), Microenvironnement et Pathologies du Cartilage (BioConnecT), Microenvironnement cellulaire et pathologie (MILPAT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Département de chirurgie orthopédique [Hôpital privé Saint Martin Caen], Hôpital Privé Saint Martin Caen |
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Cartilage
Articular MESH : Bone Marrow Aging MESH : RNA Messenger MESH : Transcription Factors MESH : Receptors Transforming Growth Factor beta MESH : Chondrogenesis MESH : Alginates MESH : Blotting Western Osteoarthritis Hip 0302 clinical medicine MESH: Aggrecans MESH: Osteoarthritis MESH : Collagen Type II Cells Cultured Regulation of gene expression Aged 80 and over 0303 health sciences [ SDV.MHEP.PHY ] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO] MESH: Bone Marrow Cells Cell Differentiation General Medicine MESH: Transcription Factors Middle Aged Cell biology MESH : Phenotype medicine.anatomical_structure Phenotype [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system 030220 oncology & carcinogenesis MESH: Alginates Disease Progression MESH: Bone Marrow MESH: Receptors Transforming Growth Factor beta MESH : Cell Differentiation MESH: Chondrogenesis Signal Transduction MESH: Cell Differentiation Blotting Western [SDV.BC]Life Sciences [q-bio]/Cellular Biology Biology MESH: Phenotype Real-Time Polymerase Chain Reaction Chondrocyte Article MESH : Chondrocytes MESH : Cartilage [ SDV.MHEP.RSOA ] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system 03 medical and health sciences Transforming Growth Factor beta2 Chondrocytes MESH: Chondrocytes medicine [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO] MESH : Aggrecans Gene silencing MESH: Blotting Western Humans [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology RNA Messenger [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry Molecular Biology Aggrecan MESH: Transforming Growth Factor beta 030304 developmental biology MESH: RNA Messenger Aged MESH: Humans [ SDV.BC ] Life Sciences [q-bio]/Cellular Biology Mesenchymal stem cell MESH : Humans MESH: Collagen Type II Chondrogenesis Molecular biology MESH : Osteoarthritis MESH : Transforming Growth Factor beta Gene Expression Regulation MESH: Cartilage Ectopic expression Geriatrics and Gerontology Transforming growth factor MESH : Bone Marrow Cells |
| Zdroj: | AGE AGE, Springer Verlag, 2013, 35 (4), pp.1105-16. 〈http://link.springer.com/article/10.1007%2Fs11357-012-9433-7〉. 〈10.1007/s11357-012-9433-7〉 Scopus-Elsevier AGE, Springer Verlag, 2013, 35 (4), pp.1105-16. ⟨10.1007/s11357-012-9433-7⟩ |
| ISSN: | 0161-9152 1574-4647 |
| DOI: | 10.1007/s11357-012-9433-7〉 |
| Popis: | International audience; Aging is one of the major risk factors of osteoarthritis. This pathology during which chondrocytes undergo modifications of their phenotype may result from alteration of transforming growth factor β (TGFβ) signaling. This study investigates the role of TGFβ response in the process of chondrocyte dedifferentiation/redifferentiation. Dedifferentiation was induced by successive passages of human articular chondrocytes, whereas their redifferentiation was performed by three-dimensional culture in alginate. Human mesenchymal stem cells were obtained from bone marrow and differentiated into chondrocyte-like phenotype by three-dimensional culture, embedded in the same scaffold. Protein and mRNA levels were analyzed by Western blot and real-time reverse transcription PCR. Regulatory mechanism was investigated using specific inhibitors (mithramycin), mRNA silencing or decoy oligonucleotides, and expression vectors. Chondrocyte dedifferentiation interfered with TGFβ signaling by decreasing TβRII mRNA and protein levels and subsequent TGFβ response. TβRII ectopic expression in passaged chondrocytes permitted to increase the expression of several matrix genes, such as aggrecan or type II collagen. Redifferentiation of passaged chondrocytes permitted to restore, at least in part, TβRII expression and was related to differentiation of human bone marrow mesenchymal stem cells toward chondrocytes, where both specific protein 1 (Sp1) and TβRII mRNA levels were increased. Moreover, Sp1 manipulation by silencing or ectopic expression and pharmacologic inhibition revealed a link between expression levels of this transcriptional factor, which is crucial for constitutive expression of TβRII in cartilage, and TGFβ response. Therefore, these data permit us to suggest an important role of TβRII expression in the maintenance of chondrocyte phenotype, which is altered with age, and bring new insights in our understanding of chondrogenesis process. |
| Databáze: | OpenAIRE |
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