An evolutionary perspective of DNA methylation patterns in skeletal tissues using a baboon model of osteoarthritis.
An evolutionary perspective of DNA methylation patterns in skeletal tissues using a baboon model of osteoarthritis.
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DOI：
10.1002/jor.24957
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发表时间：
2021-10
期刊：
影响因子：
--
通讯作者：
Stone AC
中科院分区：
文献类型：
--
作者：
Housman G;Quillen EE;Stone AC
DNA甲基化等表观遗传因素在退行性关节病骨关节炎（OA）的发展中发挥着重要作用。这些分子机制已在人类身上进行了大量研究，尽管 OA 还影响除人类外的其他几种动物，但很少有研究从进化的角度进行研究。本研究通过评估狒狒 (Papio spp.) DNA 甲基化变异与膝部 OA 发育之间的关系，并将这些发现与人类 OA 表观遗传关联进行比较，探讨了 OA 表观遗传学的演变。使用 Illumina Infinium MmethylationEPIC BeadChip 鉴定了 56 只纯种成年狒狒（28 只患有膝骨关节炎，28 只没有膝骨关节炎）的右股骨远端骨和软骨中的全基因组 DNA 甲基化模式。在组织类型之间发现了几个显着差异的甲基化位置（DMP）和区域（DMR）。在软骨中也发现了大量与 OA 相关的差异甲基化，但在骨骼中却没有，这表明软骨表观遗传学可能比骨表观遗传学对 OA 的影响更大。此外，一些含有 OA 相关 DMP 的基因与之前在人类 OA 中发现的甲基化模式重叠并表现出类似的甲基化模式，揭示了灵长类动物中进化上保守和不同的 OA 相关甲基化模式的混合。总体而言，这些发现强化了当前 OA 的病因学观点，并增强了我们对 OA 相关表观遗传机制的进化理解。这项工作进一步将狒狒确立为一种有价值的非人类灵长类 OA 模型，对狒狒的持续研究将有助于解开导致 OA 的分子机制及其进化历史。
Epigenetic factors, such as DNA methylation, play an influential role in the development of the degenerative joint disease osteoarthritis (OA). These molecular mechanisms have been heavily studied in humans, and although OA affects several other animals in addition to humans, few efforts have taken an evolutionary perspective. This study explores the evolution of OA epigenetics by assessing the relationship between DNA methylation variation and knee OA development in baboons (Papio spp.) and by comparing these findings to human OA epigenetic associations. Genome-wide DNA methylation patterns were identified in bone and cartilage of the right distal femora from 56 pedigreed, adult baboons (28 with and 28 without knee OA) using the Illumina Infinium MethylationEPIC BeadChip. Several significantly differentially methylated positions (DMPs) and regions (DMRs) were found between tissue types. Substantial OA-related differential methylation was also identified in cartilage, but not in bone, suggesting that cartilage epigenetics may be more influential in OA than bone epigenetics. Additionally, some genes containing OA-related DMPs overlap with and display methylation patterns similar to those previously identified in human OA, revealing a mixture of evolutionarily conserved and divergent OA-related methylation patterns in primates. Overall, these findings reinforce current etiological perspectives of OA and enhance our evolutionary understanding of epigenetic mechanisms associated with OA. This work further establishes baboons as a valuable nonhuman primate model of OA, and continued investigations in baboons will help to disentangle the molecular mechanisms contributing to OA and their evolutionary histories.
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影响因子：
4.5
作者：
Hernando-Herraez I;Prado-Martinez J;Garg P;Fernandez-Callejo M;Heyn H;Hvilsom C;Navarro A;Esteller M;Sharp AJ;Marques-Bonet T
通讯作者：
Marques-Bonet T
影响因子：
1.8
作者：
Cucchiarini M;de Girolamo L;Filardo G;Oliveira JM;Orth P;Pape D;Reboul P
通讯作者：
Reboul P
影响因子：
13.6
作者：
Goldring MB;Marcu KB
通讯作者：
Marcu KB
DOI：
10.1002/ajmg.10776
发表时间：
2002-10-15
期刊：
AMERICAN JOURNAL OF MEDICAL GENETICS
影响因子：
--
作者：
Goodman, FR
通讯作者：
Goodman, FR
影响因子：
2.5
作者：
Cox, Laura A.;Comuzzie, Anthony G.;VandeBerg, John L.
通讯作者：
VandeBerg, John L.