OPG/RANKL/RANK gene methylation among alcohol-induced femoral head necrosis in northern Chinese men

Abstract

Background and purpose Alcohol-induced osteonecrosis of the femoral head (ONFH) is a complex and heterogeneous disease. Genetic factors and epigenetic modifications are one of the pathogenesis of the disease. However, the influence of epigenetic factors on the disease has not been systematically studied. Our research aims to determine the methylation changes of alcohol-induced ONFH. Methods An analytical cross-sectional study of a Chinese male population (50 alcohol-induced ONFH patients and 50 controls). The EpiTYPER of the Sequenom MassARRAY platform was used to detect the DNA methylation status of 132 cytosine-phosphate-guanine (CpG) sites in the OPG/RANKL/RANK gene promoter region. Results In the whole study group, the chi-square test was used to analyze the methylation rate between the two groups, and six CpG sites were found to be different, among which OPG1_CpG_2, OPG3_CpG_4, RANK1_CpG_6, RANK3_CpG_10, RANKL2_CpG_21, and RANKL2_CpG_46 in the case group were higher than those in the control group, while OPG4_CpG_2 was lower than that in the control group. The results showed that in patients with alcohol-induced ONFH, 146 CpG sites were examined for differences in methylation levels compared with healthy controls, 32 of which were not detected, and 23 of the remaining 114 sites showed differences in methylation levels compared with alcohol-induced ONFH patients. Receiver operator characteristic (ROC) curve analysis demonstrated the methylation levels of OPG/RANKL/RANK could efficiently predict the existence of alcohol-induced ONFH. Conclusion Our study of Chinese men suggests that several CpG sites in the OPG/RANKL/RANK gene in peripheral blood leukocytes of patients with alcohol-induced ONFH are in an abnormal methylation state (hypermethylation tended to be more frequent).

Genome-wide association study for loin muscle area of commercial crossbred pigs

“…The myocardin ( MYOCD ) gene locus near the MARC0094338 on SSC 12 is associated with lung cancer [ 44 ], the ARho GTPase activating protein 44 ( ARHGAP44 ) gene is associated with tumors [ 45 ], the ElaC Ribonuclease Z 2 ( ELAC2 ) gene is reported to be associated with prostate cancer [ 46 ], the mitogen-activated protein kinase kinase 4 ( MAP2K4 ) gene is associated with breast cancer [ 47 ], F-Box protein 4 ( FBXO4 ) located near ASGA0072817 on SSC 16 is associated with cancer [ 48 ], and fibrillarin like 1 ( FBLL1 ) located near WU_ 10.2_14_144250775 on SSC 14 is associated with liver cancer [ 49 ]. In addition, the arginyl-TRNA synthetase 1 ( RARS1 ) gene has been shown to be associated with various diseases of the central nervous system [ 50 ], slit guidance ligand 3 ( SLIT3 ) located near ALGA0090878 on SSC16 is associated with the bone loss [ 51 ], and the receptor activator of NF-Kb 3 ( RANK3 ) gene is associated with alcoholic femoral head necrosis [ 52 ]. While these genes are currently poorly studied in pigs, but do not exclude the possibility of their association with LMA, the OXCT1 gene has been well-documented to play a pivotal role in supporting malignancy [ 53 ], with studies in China pointing to its association with adipose development.…”

“…with liver cancer [49]. In addition, the RARS1 gene has been shown to be associated with various diseases of the central nervous system [50], SLIT3 located near ALGA0090878 on SSC16 is associated with the bone loss [51], and the RANK3 gene is associated with alcoholic femoral head necrosis [52]. While these genes are currently poorly studied in pigs, but do not exclude the possibility of their association with LMA, the OXCT1 gene has been well-documented to play a pivotal role in supporting malignancy [53], with studies in China pointing to its association with adipose development.…”

Avascular necrosis of bone tissue: Definition, epidemiology, types, risk factors, pathogenesis of the disease. Analytical review of the literature

“…Патогенез развития АН, индуцированного алкоголем, аналогичен таковому при использовании ГК и складывается из ингибирования пролиферации и дифференциации остеобластов, апоптоза остеоцитов, стимуляции адипогенеза взамен остеобластогенеза, увеличения числа и размера жировых клеток в костном мозге, увеличения концентрации триглицеридов и холестерина в плазме крови [3,10,[201][202][203][204].…”

Gadus morhua Eggs Sialoglycoprotein Prevent Estrogen Deficiency-Induced High Bone Turnover by Controlling OPG/RANKL/TRAF6 Pathway and Serum Metabolism

“…Osteoblasts secrete various osteogenic active substances, regulate extracellular matrix maturation, and promote bone formation. The signal transformation of bone marrow mesenchymal stromal cells differentiation in patients with osteoporosis in vivo results in increased adipocyte differentiation ( 14 ), decreased osteoblast differentiation, leading to lower expression of OPG, resulting in bone loss ( 15 ). The influence of adipocyte differentiation can be harnessed pharmacologically to osteoporosis treatment.…”