Assessment of DNA methylation patterns in the bone and cartilage of a nonhuman primate model of osteoarthritis

Abstract

Objective: Osteoarthritis (OA) impacts humans and several other animals. Thus, the mechanisms underlying this disorder, such as specific skeletal tissue DNA methylation patterns, may be evolutionary conserved. However, associations between methylation and OA have not been readily studied in nonhuman animals. Baboons serve as important models of disease and develop OA at rates similar to those in humans. Therefore, this study investigated the associations between methylation and OA in baboons to advance the evolutionary understanding of OA.Design: Trabecular bone and cartilage was collected from the medial condyles of adult female baboon femora, five with and five without knee OA. The Infinium HumanMethylation450BeadChip (450K array) was used to identify DNA methylation patterns in these tissues.Results: Approximately 44% of the 450K array probes reliably align to the baboon genome, contain a CpG site of interest, and maintain a wide distribution throughout the genome. Of the two filtering methods tested, both identified significantly differentially methylated positions (DMPs) between healthy and OA individuals in cartilage tissues, and some of these patterns overlap with those previously identified in humans. Conversely, no DMPs were found between tissue types or between disease states in bone tissues. Conclusions:Overall, the 450K array can be used to measure genome-wide DNA methylation in baboon tissues and identify significant associations with complex traits. The results of this study indicate that some DNA methylation patterns associated with OA are evolutionarily conserved, while others are not. This warrants further investigation in a larger and more phylogenetically diverse sample set.

An evolutionary perspective of DNA methylation patterns in skeletal tissues using a baboon model of osteoarthritis

“…Additionally, our study identified substantially more DMPs than a previous investigation of baboon OA. 17 Although this prior study used the 450K array, the total number of sites examined was similar, suggesting that increased power was primarily due to an increased sample size. The expansion of DMP findings allowed for subsequent analyses of DMRs which showed similar number trends and gene associations, further confirming the DMP results and their functional implications.…”

“…Baboons were classified as having healthy or OA knees as previously described. 17 Briefly, each specimen was assigned an OA severity score based on macroscopic inspection of the articular surface cartilage of the distal femora: Grade 1 is unaffected, Grade 2 is mild OA (cartilage fibrillation), Grade 3 is moderate OA (cartilage lesions), and Grade 4 is advanced OA (eburnation). 12 For each sample, a cartilage scraping was obtained from the inferior aspect of the medial condyle on the right distal femur, and a trabecular bone core was obtained from a transverse plane through the center of the same condyle such that the articular surface remained preserved.…”

“…Furthermore, in captive colonies of baboons, environmental factors can be regulated and controlled, thus enabling more detailed investigations of the molecular mechanisms contributing to OA pathogenesis than can be achieved in humans. 12,14 Lastly, because of their evolutionary proximity to humans, using baboons as an animal model of OA will advance the evolutionary understanding of this disease, 17 a perspective that has not been readily explored. The similar manifestations of OA in humans and baboons as compared with less similar manifestations of OA between humans and more phylogenetically distant animals, 11 suggests that OA susceptibility and pathogenesis has undergone different waves of evolutionary conservation and divergence across species.…”

Analysis and annotation of genome-wide DNA methylation patterns in two nonhuman primate species using the Infinium Human Methylation 450K and EPIC BeadChips

“…Again, position of potential mismatches was not further evaluated. The same filtering approach as proposed by Ong et al [19] was subsequently also used for a study on osteoarthritis using baboon samples which concluded that a total of 44 % of probes on the 450K BeadChip could be reliably used [20].…”

“…Seventy-three percent of the probes designed to the human genome mapped to the bonobo genome, 72%-77% to chimpanzee, 61% to gorilla and 44% to orangutan genomes [17,18]. Studies were also performed in monkeys of the cynomolgus macaque species (Macaca fascicularis) [19], rhesus macaque (Macaca mulata, MM) [18] and baboon [20]. For example, using different selection criteria for probes yielding reliable signals, 61% of human probes were mapped and annotated to the Macaca fascicularis genome and subsequently used to study the impact of birth weight on gene methylation and expression in Macaca fascicularis [21].…”