Transcriptomic and epigenomic analyses uncovered Lrrc15 as a contributing factor to cartilage damage in osteoarthritis.
Transcriptomic and epigenomic analyses uncovered Lrrc15 as a contributing factor to cartilage damage in osteoarthritis.
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DOI：
10.1038/s41598-021-00269-8
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发表时间：
2021-10-26
影响因子：
4.6
通讯作者：
Otero M
中科院分区：
文献类型：
--
作者：
Singh P;Wang M;Mukherjee P;Lessard SG;Pannellini T;Carballo CB;Rodeo SA;Goldring MB;Otero M
在骨关节炎（OA）中，关节软骨细胞显示与表观基因组改变相关的表型和功能变化。这些变化有助于疾病进展，其特征在于失调的修复过程和异常的细胞外基质重塑，导致软骨降解。最近使用创伤后OA小鼠模型的研究强调了DNA羟甲基化（5hmC）的变化对OA进展的贡献。在这里，我们整合了转录组和表观基因组分析后，诱导骨关节炎的软骨显示，骨关节炎的结构进展伴随着早期转录组和显着的DNA甲基化（5mC）的变化，在软骨细胞。这些变化随着时间的推移而积累，并与发育过程的重演有关，包括软骨发育，软骨细胞肥大和骨化。我们的综合分析还发现，Lrrc15是差异甲基化和表达在OA软骨，它可能有助于软骨细胞的功能和表型改变，可能协调应激反应和失调的细胞外基质重塑。
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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影响因子：
28.2
作者：
Dominguez, Claudia X.;Mueller, Soren;Turley, Shannon J.
通讯作者：
Turley, Shannon J.
影响因子：
2.7
作者：
Chen L;Zhang Y;Rao Z;Zhang J;Sun Y
通讯作者：
Sun Y
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：
64.8
作者：
Huttlin EL;Bruckner RJ;Paulo JA;Cannon JR;Ting L;Baltier K;Colby G;Gebreab F;Gygi MP;Parzen H;Szpyt J;Tam S;Zarraga G;Pontano-Vaites L;Swarup S;White AE;Schweppe DK;Rad R;Erickson BK;Obar RA;Guruharsha KG;Li K;Artavanis-Tsakonas S;Gygi SP;Harper JW
通讯作者：
Harper JW
DOI：
10.1007/978-1-0716-0989-7_14
发表时间：
2021-01-01
期刊：
OSTEOPOROSIS AND OSTEOARTHRITIS, 2 EDITION
影响因子：
--
作者：
Culley, Kirsty L.;Singh, Purva;Otero, Miguel
通讯作者：
Otero, Miguel