Abstract
Objective 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.
Methods 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.
Results 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.
Conclusions 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.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
Author Notes: Genevieve Housman is currently affiliated with the University of Chicago, and Ellen E. Quillen is currently affiliated with Wake Forest School of Medicine.
Funding: This work was supported by the National Institutes of Health (P01HL028972 to Anthony G. Comuzzie); the Leakey Foundation (Research Grant for Doctoral Students to G.H.); the Wenner-Gren Foundation (Gr. 9310 to G.H.); the Nacey Maggioncalda Foundation (James F. Nacey Fellowship to G.H.); the International Primatological Society (to G.H.); Sigma Xi (Grant-in-Aid of Research to G.H.); the ASU Center for Evolution and Medicine (Venture Fund to G.H.); and the ASU Graduate Research and Support Program (to G.H.). Additionally, this investigation used resources that were supported by the Southwest National Primate Research Center grant P51OD011133 from the Office of Research Infrastructure Programs, National Institutes of Health.