Changes in DNA methylation accompany changes in gene expression during chondrocyte hypertrophic differentiation in vitro.
Changes in DNA methylation accompany changes in gene expression during chondrocyte hypertrophic differentiation in vitro.
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DOI：
10.1111/nyas.14494
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发表时间：
2021-04
影响因子：
5.2
通讯作者：
Otero M
中科院分区：
文献类型：
--
作者：
Singh P;Lessard SG;Mukherjee P;Rourke B;Otero M
在骨关节炎期间，关节软骨细胞经历了类似于生长板软骨细胞特有的发育模式的表型变化。这些表型改变导致肥大样表型，其特征是细胞外基质成分的产生改变和胶原酶活性增加，这反过来导致骨性关节炎的软骨破坏。最近的研究表明，骨性关节炎的表型不稳定性和基因表达异常与DNA甲基化模式的改变有关。随后的努力旨在确定DNA甲基化在OA疾病中具有功能影响的变化，以潜在地发现治疗靶点。在这里，我们将模拟软骨细胞肥大的体外3D/颗粒培养系统与RNA测序(RNA-Seq)和增强型亚硫酸氢盐测序(ERRBS)配对，以识别经历肥大样分化的小鼠原代关节软骨细胞的转录和表观基因组变化。我们在体外发现了与肥大相关的DNA甲基化模式的变化。整合RNA-Seq和ERRBS数据集确定了甲基化变化和基因表达之间的关联。我们的综合分析表明，在体外，关节软骨细胞的肥大分化伴随着转录和表观基因组的变化。我们相信，我们的综合方法有可能发现治疗干预的新靶点。骨关节炎(OA)关节软骨细胞的表型不稳定性和基因表达异常与DNA甲基化模式的改变有关。在这里，我们(A)使用3D/颗粒培养系统(B)在体外诱导肥大，(C)进行RNA测序(RNA-Seq)和增强亚硫酸氢盐测序(ERRBS)，并结合(D)比较非肥大和肥大细胞的综合生物信息学分析来识别和解释与小鼠原代关节软骨细胞肥大样分化相关的转录和表观组学变化。使用BioRender.com创建
During osteoarthritis (OA), articular chondrocytes undergo phenotypic changes that resemble developmental patterns characteristic of growth plate chondrocytes. These phenotypic alterations lead to a hypertrophy-like phenotype characterized by altered production of extracellular matrix constituents and increased collagenase activity, which in turn results in cartilage destruction in OA disease. Recent studies have shown that the phenotypic instability and dysregulated gene expression in OA are associated with changes in DNA methylation patterns. Subsequent efforts have aimed to identify changes in DNA methylation with functional impact in OA disease, to potentially uncover therapeutic targets. Here, we paired an in vitro 3D/pellet culture system that mimics chondrocyte hypertrophy with RNA sequencing (RNA-Seq) and enhanced reduced representation of bisulfite sequencing (ERRBS) to identify transcriptomic and epigenomic changes in murine primary articular chondrocytes undergoing hypertrophy-like differentiation. We identified hypertrophy-associated changes in DNA methylation patterns in vitro. Integration of RNA-Seq and ERRBS datasets identified associations between changes in methylation and gene expression. Our integrative analyses showed that hypertrophic differentiation of articular chondrocytes is accompanied by transcriptomic and epigenomic changes in vitro. We believe that our integrative approaches have the potential to uncover new targets for therapeutic intervention. The phenotypic instability and dysregulated gene expression of articular chondrocytes in osteoarthritis (OA) are associated with changes in DNA methylation patterns. Here, we (A) used 3D/pellet culture systems to (B) induce hypertrophy in vitro and (C) perform RNA sequencing (RNA-Seq) and enhanced reduced representation of bisulfite sequencing (ERRBS) paired with (D) integrative bioinformatic analyses comparing non-hypertrophic and hypertrophic cells to identify and interpret transcriptomic and epigenomic changes associated with the hypertrophy-like differentiation of murine primary articular chondrocytes. Created with BioRender.com
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影响因子：
12.3
作者：
Akalin A;Kormaksson M;Li S;Garrett-Bakelman FE;Figueroa ME;Melnick A;Mason CE
通讯作者：
Mason CE
影响因子：
4.6
作者：
Barter, Matt J.;Bui, Catherine;Young, David A.
通讯作者：
Young, David A.
骨关节炎的炎症。
影响因子：
5.1
作者：
Goldring MB;Otero M
通讯作者：
Otero M
影响因子：
--
作者：
Hashimoto, Ko;Oreffo, Richard O. C.;Gibson, Marc B.;Goldring, Mary B.;Roach, Helmtrud I.
通讯作者：
Roach, Helmtrud I.
影响因子：
1.2
作者：
Garrett-Bakelman, Francine E.;Sheridan, Caroline K.;Melnick, Ari M.
通讯作者：
Melnick, Ari M.