The Lysine Specific Demethylase-1 Negatively Regulates the <i>COL9A1</i> Gene in Human Articular Chondrocytes
Osteoarthritis (OA) is a degenerative disease of the joints which is associated with an impaired production of the cartilage matrix by the chondrocytes. Here, we investigated the role of Lysine-Specific Demethylase-1 (LSD1), a chromatin remodeling enzyme whose role in articular chondrocytes was prev...
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| Format: | Article |
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MDPI AG
2020-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/17/6322 |
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| author | Anne-Laure Durand Alexandre Dufour Elisabeth Aubert-Foucher Christine Oger-Desfeux Marielle Pasdeloup Sebastien Lustig Elvire Servien Gualter Vaz Emeline Perrier-Groult Frederic Mallein-Gerin Jerome E. Lafont |
| author_facet | Anne-Laure Durand Alexandre Dufour Elisabeth Aubert-Foucher Christine Oger-Desfeux Marielle Pasdeloup Sebastien Lustig Elvire Servien Gualter Vaz Emeline Perrier-Groult Frederic Mallein-Gerin Jerome E. Lafont |
| author_sort | Anne-Laure Durand |
| collection | DOAJ |
| description | Osteoarthritis (OA) is a degenerative disease of the joints which is associated with an impaired production of the cartilage matrix by the chondrocytes. Here, we investigated the role of Lysine-Specific Demethylase-1 (LSD1), a chromatin remodeling enzyme whose role in articular chondrocytes was previously associated with a catabolic activity and which is potentially involved during OA. Following a loss of function strategy and RNA sequencing analysis, we detail the genes which are targeted by LSD1 in human articular chondrocytes and identify <i>COL9A1</i>, a gene encoding the α1 chain of the cartilage-specific type IX collagen, as negatively regulated by LSD1. We show that LSD1 interacts with the transcription factor SOX9 and is recruited to the promoter of <i>COL9A1</i>. Interestingly, we observe that OA cartilage displays stronger LSD1 immunostaining compared with normal, and we demonstrate that the depletion of <i>LSD1</i> in OA chondrocytes prevents the decrease in <i>COL9A1</i> following Il-1β treatment. These results suggest LSD1 is a new regulator of the anabolic activity of articular chondrocytes potentially destabilizing the cartilage matrix, since it negatively regulates <i>COL9A1</i>, a gene encoding a crucial anchoring collagen molecule. This newly identified role played by LSD1 may thus participate in the alteration of the cartilage matrix during OA. |
| first_indexed | 2024-03-10T16:41:20Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T16:41:20Z |
| publishDate | 2020-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-e8e8c4b21cbb466881f959eb5d96acd32023-11-20T12:03:15ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-08-012117632210.3390/ijms21176322The Lysine Specific Demethylase-1 Negatively Regulates the <i>COL9A1</i> Gene in Human Articular ChondrocytesAnne-Laure Durand0Alexandre Dufour1Elisabeth Aubert-Foucher2Christine Oger-Desfeux3Marielle Pasdeloup4Sebastien Lustig5Elvire Servien6Gualter Vaz7Emeline Perrier-Groult8Frederic Mallein-Gerin9Jerome E. Lafont10CNRS UMR 5305 Laboratory of Tissue Biology and Therapeutic Engineering, Université Claude Bernard Lyon1, Univ Lyon, 69367 Lyon, FranceCNRS UMR 5305 Laboratory of Tissue Biology and Therapeutic Engineering, Université Claude Bernard Lyon1, Univ Lyon, 69367 Lyon, FranceCNRS UMR 5305 Laboratory of Tissue Biology and Therapeutic Engineering, Université Claude Bernard Lyon1, Univ Lyon, 69367 Lyon, FrancePRABI-AMSB, Batiment Mendel, Campus de la Doua, Université Claude Bernard Lyon1, University Lyon, 69622 Villeurbanne CEDEX, FranceCNRS UMR 5305 Laboratory of Tissue Biology and Therapeutic Engineering, Université Claude Bernard Lyon1, Univ Lyon, 69367 Lyon, FranceFIFA Medical Center of Excellence Orthopaedic Surgery and Sports Medicine Department, Croix-Rousse Hospital, Hospices Civils de Lyon, 103 grande rue de la Croix-Rousse 69317 Lyon CEDEX 04, France and IFSTTAR, LBMC UMR_T9406 Univ Lyon, Claude Bernard Lyon 1 University, 69317 Lyon, FranceFIFA Medical Center of Excellence, Orthopaedic Surgery and Sports Medicine Department, Croix-Rousse Hospital, Hospices Civils de Lyon, 103 grande rue de la Croix-Rousse 69317 Lyon CEDEX 04, France; LIBM-EA 7424, Interuniversity Laboratory of Biology of Mobility, Claude Bernard Lyon 1 University, 69317 Lyon, FranceOrthopaedic Surgery Department, CMCR les Massues, Croix rouge française, 92 rue Edmond Locard, 69005 Lyon, FranceCNRS UMR 5305 Laboratory of Tissue Biology and Therapeutic Engineering, Université Claude Bernard Lyon1, Univ Lyon, 69367 Lyon, FranceCNRS UMR 5305 Laboratory of Tissue Biology and Therapeutic Engineering, Université Claude Bernard Lyon1, Univ Lyon, 69367 Lyon, FranceCNRS UMR 5305 Laboratory of Tissue Biology and Therapeutic Engineering, Université Claude Bernard Lyon1, Univ Lyon, 69367 Lyon, FranceOsteoarthritis (OA) is a degenerative disease of the joints which is associated with an impaired production of the cartilage matrix by the chondrocytes. Here, we investigated the role of Lysine-Specific Demethylase-1 (LSD1), a chromatin remodeling enzyme whose role in articular chondrocytes was previously associated with a catabolic activity and which is potentially involved during OA. Following a loss of function strategy and RNA sequencing analysis, we detail the genes which are targeted by LSD1 in human articular chondrocytes and identify <i>COL9A1</i>, a gene encoding the α1 chain of the cartilage-specific type IX collagen, as negatively regulated by LSD1. We show that LSD1 interacts with the transcription factor SOX9 and is recruited to the promoter of <i>COL9A1</i>. Interestingly, we observe that OA cartilage displays stronger LSD1 immunostaining compared with normal, and we demonstrate that the depletion of <i>LSD1</i> in OA chondrocytes prevents the decrease in <i>COL9A1</i> following Il-1β treatment. These results suggest LSD1 is a new regulator of the anabolic activity of articular chondrocytes potentially destabilizing the cartilage matrix, since it negatively regulates <i>COL9A1</i>, a gene encoding a crucial anchoring collagen molecule. This newly identified role played by LSD1 may thus participate in the alteration of the cartilage matrix during OA.https://www.mdpi.com/1422-0067/21/17/6322articular chondrocytestype IX collagenlysine demethylaseosteoarthritis |
| spellingShingle | Anne-Laure Durand Alexandre Dufour Elisabeth Aubert-Foucher Christine Oger-Desfeux Marielle Pasdeloup Sebastien Lustig Elvire Servien Gualter Vaz Emeline Perrier-Groult Frederic Mallein-Gerin Jerome E. Lafont The Lysine Specific Demethylase-1 Negatively Regulates the <i>COL9A1</i> Gene in Human Articular Chondrocytes International Journal of Molecular Sciences articular chondrocytes type IX collagen lysine demethylase osteoarthritis |
| title | The Lysine Specific Demethylase-1 Negatively Regulates the <i>COL9A1</i> Gene in Human Articular Chondrocytes |
| title_full | The Lysine Specific Demethylase-1 Negatively Regulates the <i>COL9A1</i> Gene in Human Articular Chondrocytes |
| title_fullStr | The Lysine Specific Demethylase-1 Negatively Regulates the <i>COL9A1</i> Gene in Human Articular Chondrocytes |
| title_full_unstemmed | The Lysine Specific Demethylase-1 Negatively Regulates the <i>COL9A1</i> Gene in Human Articular Chondrocytes |
| title_short | The Lysine Specific Demethylase-1 Negatively Regulates the <i>COL9A1</i> Gene in Human Articular Chondrocytes |
| title_sort | lysine specific demethylase 1 negatively regulates the i col9a1 i gene in human articular chondrocytes |
| topic | articular chondrocytes type IX collagen lysine demethylase osteoarthritis |
| url | https://www.mdpi.com/1422-0067/21/17/6322 |
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