دورية أكاديمية

The Lysine Specific Demethylase-1 Negatively Regulates the COL9A1 Gene in Human Articular Chondrocytes.

التفاصيل البيبلوغرافية
العنوان: The Lysine Specific Demethylase-1 Negatively Regulates the COL9A1 Gene in Human Articular Chondrocytes.
المؤلفون: Durand AL; CNRS UMR 5305 Laboratory of Tissue Biology and Therapeutic Engineering, Université Claude Bernard Lyon1, Univ Lyon, 69367 Lyon, France., Dufour A; CNRS UMR 5305 Laboratory of Tissue Biology and Therapeutic Engineering, Université Claude Bernard Lyon1, Univ Lyon, 69367 Lyon, France., Aubert-Foucher E; CNRS UMR 5305 Laboratory of Tissue Biology and Therapeutic Engineering, Université Claude Bernard Lyon1, Univ Lyon, 69367 Lyon, France., Oger-Desfeux C; PRABI-AMSB, Batiment Mendel, Campus de la Doua, Université Claude Bernard Lyon1, University Lyon, 69622 Villeurbanne CEDEX, France., Pasdeloup M; CNRS UMR 5305 Laboratory of Tissue Biology and Therapeutic Engineering, Université Claude Bernard Lyon1, Univ Lyon, 69367 Lyon, France., Lustig S; FIFA 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, France., Servien E; FIFA 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, France., Vaz G; Orthopaedic Surgery Department, CMCR les Massues, Croix rouge française, 92 rue Edmond Locard, 69005 Lyon, France., Perrier-Groult E; CNRS UMR 5305 Laboratory of Tissue Biology and Therapeutic Engineering, Université Claude Bernard Lyon1, Univ Lyon, 69367 Lyon, France., Mallein-Gerin F; CNRS UMR 5305 Laboratory of Tissue Biology and Therapeutic Engineering, Université Claude Bernard Lyon1, Univ Lyon, 69367 Lyon, France., Lafont JE; CNRS UMR 5305 Laboratory of Tissue Biology and Therapeutic Engineering, Université Claude Bernard Lyon1, Univ Lyon, 69367 Lyon, France.
المصدر: International journal of molecular sciences [Int J Mol Sci] 2020 Aug 31; Vol. 21 (17). Date of Electronic Publication: 2020 Aug 31.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Basel, Switzerland : MDPI, [2000-
مواضيع طبية MeSH: Gene Expression Regulation*, Cartilage, Articular/*metabolism , Chondrocytes/*metabolism , Collagen Type IX/*genetics , Histone Demethylases/*metabolism , Osteoarthritis/*metabolism, Adult ; Aged ; Aged, 80 and over ; Cartilage, Articular/cytology ; Case-Control Studies ; Cells, Cultured ; Chondrocytes/cytology ; Collagen Type IX/metabolism ; Histone Demethylases/genetics ; Humans ; Lysine/chemistry ; Lysine/genetics ; Middle Aged ; Osteoarthritis/genetics ; Osteoarthritis/pathology ; Promoter Regions, Genetic
مستخلص: 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 COL9A1 , 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 COL9A1 . Interestingly, we observe that OA cartilage displays stronger LSD1 immunostaining compared with normal, and we demonstrate that the depletion of LSD1 in OA chondrocytes prevents the decrease in COL9A1 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 COL9A1 , 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.
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فهرسة مساهمة: Keywords: articular chondrocytes; lysine demethylase; osteoarthritis; type IX collagen
المشرفين على المادة: 0 (COL9A1 protein, human)
0 (Collagen Type IX)
EC 1.14.11.- (Histone Demethylases)
EC 1.5.- (KDM1A protein, human)
K3Z4F929H6 (Lysine)
تواريخ الأحداث: Date Created: 20200904 Date Completed: 20210325 Latest Revision: 20210325
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC7504057
DOI: 10.3390/ijms21176322
PMID: 32878268
قاعدة البيانات: MEDLINE
الوصف
تدمد:1422-0067
DOI:10.3390/ijms21176322