TY - JOUR
T1 - DNA methylation of bone morphogenetic protein 7 in leukocytes as a possible biomarker for hand osteoarthritis
T2 - A pilot study
AU - Kuroiwa, Takashi
AU - Tsuboi, Yoshiki
AU - Michikawa, Takehiro
AU - Tajima, Kaori
AU - Uraya, Yuki
AU - Maeda, Atsushi
AU - Shizu, Kanae
AU - Suzuki, Katsuji
AU - Suzuki, Koji
AU - Kawano, Yusuke
AU - Fujita, Nobuyuki
N1 - Publisher Copyright:
© 2024 The Author(s). Journal of Orthopaedic Research® published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society.
PY - 2025/1
Y1 - 2025/1
N2 - Hand osteoarthritis (HOA), characterized by an earlier onset age and reduced susceptibility to mechanical stress compared with knee and hip osteoarthritis, is considered a suitable disease for identifying predictive biomarkers of osteoarthritis. In particular, DNA methylation variants, expected to contribute to HOA susceptibility, hold potential as osteoarthritis biomarkers. In this study, leukocyte DNA methylation patterns were analyzed in blood samples from patients with HOA, aiming to identify disease-specific biomarkers for osteoarthritis. Using DNA methylation microarrays, we analyzed samples from three subjects with HOA and three age- and gender-matched healthy individuals. For validation, pyrosequencing analysis was conducted using samples from 16 to 9 subjects with and without HOA, respectively. From 735,026 probes in the DNA methylation array, the Top 100 CpG sites associated with HOA, based on low adjusted P-values, including those targeting bone morphogenetic protein 7 (BMP7), SBF2-AS1, PLOD2, ICOS, and CSF1R were identified. Validation analysis revealed significantly higher methylation levels in the BMP7-related site in the HOA group compared with the control group, even after adjusting for age, gender, and body mass index (p = 0.037). In contrast, no significant difference was observed in the other selected CpG sites between the HOA and control groups. This study highlights the significantly increased frequency of methylation at the specific BMP7 site in leukocytes of patients with HOA, suggesting its potential as a biomarker for HOA. Measurement of methylation levels at the CpG sites identified in this study offers a potential approach to prevent future osteoarthritis progression, providing valuable insights into disease management.
AB - Hand osteoarthritis (HOA), characterized by an earlier onset age and reduced susceptibility to mechanical stress compared with knee and hip osteoarthritis, is considered a suitable disease for identifying predictive biomarkers of osteoarthritis. In particular, DNA methylation variants, expected to contribute to HOA susceptibility, hold potential as osteoarthritis biomarkers. In this study, leukocyte DNA methylation patterns were analyzed in blood samples from patients with HOA, aiming to identify disease-specific biomarkers for osteoarthritis. Using DNA methylation microarrays, we analyzed samples from three subjects with HOA and three age- and gender-matched healthy individuals. For validation, pyrosequencing analysis was conducted using samples from 16 to 9 subjects with and without HOA, respectively. From 735,026 probes in the DNA methylation array, the Top 100 CpG sites associated with HOA, based on low adjusted P-values, including those targeting bone morphogenetic protein 7 (BMP7), SBF2-AS1, PLOD2, ICOS, and CSF1R were identified. Validation analysis revealed significantly higher methylation levels in the BMP7-related site in the HOA group compared with the control group, even after adjusting for age, gender, and body mass index (p = 0.037). In contrast, no significant difference was observed in the other selected CpG sites between the HOA and control groups. This study highlights the significantly increased frequency of methylation at the specific BMP7 site in leukocytes of patients with HOA, suggesting its potential as a biomarker for HOA. Measurement of methylation levels at the CpG sites identified in this study offers a potential approach to prevent future osteoarthritis progression, providing valuable insights into disease management.
KW - BMP7
KW - DNA methylation microarray
KW - biomarkers
KW - hand osteoarthritis
KW - leukocyte
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U2 - 10.1002/jor.25963
DO - 10.1002/jor.25963
M3 - Article
C2 - 39182186
AN - SCOPUS:85201966899
SN - 0736-0266
VL - 43
SP - 84
EP - 93
JO - Journal of Orthopaedic Research
JF - Journal of Orthopaedic Research
IS - 1
ER -