Transcriptomic and epigenomic analyses uncovered Lrrc15 as a contributing factor to cartilage damage in osteoarthritis.

Autor: Singh P; Hospital for Special Surgery, HSS Research Institute, New York, NY, 10021, USA., Wang M; Hospital for Special Surgery, HSS Research Institute, New York, NY, 10021, USA.; School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, China., Mukherjee P; Weill Cornell Medicine, New York, NY, 10021, USA., Lessard SG; Hospital for Special Surgery, HSS Research Institute, New York, NY, 10021, USA., Pannellini T; Hospital for Special Surgery, HSS Research Institute, New York, NY, 10021, USA., Carballo CB; Hospital for Special Surgery, HSS Research Institute, New York, NY, 10021, USA., Rodeo SA; Hospital for Special Surgery, HSS Research Institute, New York, NY, 10021, USA.; Weill Cornell Medicine, New York, NY, 10021, USA., Goldring MB; Hospital for Special Surgery, HSS Research Institute, New York, NY, 10021, USA.; Weill Cornell Medicine, New York, NY, 10021, USA., Otero M; Hospital for Special Surgery, HSS Research Institute, New York, NY, 10021, USA. OteroM@hss.edu.; Weill Cornell Medicine, New York, NY, 10021, USA. OteroM@hss.edu.; Hospital for Special Surgery, Orthopedic Soft Tissue Research Program, HSS Research Institute, Room 603, 535 East 70th Street, New York, NY, 10021, USA. OteroM@hss.edu.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2021 Oct 26; Vol. 11 (1), pp. 21107. Date of Electronic Publication: 2021 Oct 26.
DOI: 10.1038/s41598-021-00269-8
Abstrakt: In osteoarthritis (OA), articular chondrocytes display phenotypic and functional changes associated with epigenomic alterations. These changes contribute to the disease progression, which is characterized by dysregulated reparative processes and abnormal extracellular matrix remodeling leading to cartilage degradation. Recent studies using a murine model of posttraumatic OA highlighted the contribution of changes in DNA hydroxymethylation (5hmC) to OA progression. Here, we integrated transcriptomic and epigenomic analyses in cartilage after induction of OA to show that the structural progression of OA is accompanied by early transcriptomic and pronounced DNA methylation (5mC) changes in chondrocytes. These changes accumulate over time and are associated with recapitulation of developmental processes, including cartilage development, chondrocyte hypertrophy, and ossification. Our integrative analyses also uncovered that Lrrc15 is differentially methylated and expressed in OA cartilage, and that it may contribute to the functional and phenotypic alterations of chondrocytes, likely coordinating stress responses and dysregulated extracellular matrix remodeling.
(© 2021. The Author(s).)
Databáze: MEDLINE
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