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

Purva Singh; Mengying Wang; Piali Mukherjee; Samantha G. Lessard; Tania Pannellini; Camila B. Carballo; Scott A. Rodeo; Mary B. Goldring; Miguel Otero

doi:10.1038/s41598-021-00269-8

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

Purva Singh, Mengying Wang, Piali Mukherjee, Samantha G. Lessard, Tania Pannellini, Camila B. Carballo, Scott A. Rodeo, Mary B. Goldring, Miguel Otero

Hospital for Special Surgery

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9 Citations (Scopus)

Abstract

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.

Original language	English
Article number	21107
Journal	Scientific Reports
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41598-021-00269-8
Publication status	Published - Dec 2021

Bibliographical note

Publisher Copyright:
© 2021, The Author(s).

Funding

This work was supported by National Institutes of Health Grant R21 AG049980 (M.O.). M.W. received support from a Scholarship from the Xi’an Jiaotong University. The authors are also grateful to the Tow Foundation, which provided support for the David Z. Rosensweig Genomics Research Center, Giammaria Giuliani, Marina Kellen French and the Anna-Maria and Stephen Kellen French Foundation, the Ira W. DeCamp Foundation, and the Ambrose Monell Foundation. This work was supported by National Institutes of Health Grant R21 AG049980 (M.O.). M.W. received support from a Scholarship from the Xi’an Jiaotong University. The authors are also grateful to the Tow Foundation, which provided support for the David Z. Rosensweig Genomics Research Center, Giammaria Giuliani, Marina Kellen French and the Anna-Maria and Stephen Kellen French Foundation, the Ira W. DeCamp Foundation, and the Ambrose Monell Foundation. Technical support was provided by the Epigenomics Core of Weill Cornell Medicine, and the HSS Research Institute Histopathology Service. The authors are thankful to Ms. Orla O’Shea for her help with the LRRC15 immunostaining, and to Dr. Carl Blobel’s laboratory for their help with the LRRC15 immunoblotting.

Funders	Funder number
HSS Research Institute Histopathology Service
Stephen Kellen French Foundation
National Institutes of Health
National Institute on Aging	R21AG049980
Ambrose Monell Foundation
Ira W. DeCamp Foundation
Tow Foundation
Xi’an Jiaotong University

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title = "Transcriptomic and epigenomic analyses uncovered Lrrc15 as a contributing factor to cartilage damage in osteoarthritis",

abstract = "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.",

author = "Purva Singh and Mengying Wang and Piali Mukherjee and Lessard, {Samantha G.} and Tania Pannellini and Carballo, {Camila B.} and Rodeo, {Scott A.} and Goldring, {Mary B.} and Miguel Otero",

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AU - Lessard, Samantha G.

AU - Pannellini, Tania

AU - Carballo, Camila B.

AU - Rodeo, Scott A.

AU - Goldring, Mary B.

AU - Otero, Miguel

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Y1 - 2021/12

N2 - 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.

AB - 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.

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

Abstract

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