Genome-wide DNA methylation profiling of hip articular cartilage identifies differentially methylated loci associated with osteonecrosis of the femoral head

Wu, Junlong; Du, Yanan; Song, Jidong; Dang, Xiaoqian; Wang, Kunzheng; Wen, Yan; Zhang, Feng; Liu, Ruiyu

doi:10.1016/j.bone.2019.06.021

Cited by 12 publications

(10 citation statements)

References 43 publications

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“…DNA methylation is an epigenetic regulation form with important roles in gene expression and tissue development ( Zhang et al, 2019 ). Although bone DNA methylation has been analyzed in human ( Wu et al, 2019 ), baboon femora ( Housman et al, 2017 ), and rat ( Villagra et al, 2002 ; Nagaoka et al, 2019 ), to our knowledge, this is the first systematic comparison of genome-wide DNA methylation profiles of bilateral mandibular condyle in chickens. In the present study, bilateral mandibular condyles of genome-wide methylation patterns were similar in functional genomic regions.…”

Section: Discussionmentioning

confidence: 99%

Analysis of DNA Methylation Profiles in Mandibular Condyle of Chicks With Crossed Beaks Using Whole-Genome Bisulfite Sequencing

Shi

Bai

et al. 2021

Front. Genet.

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Crossed beaks have been observed in at least 12 chicken strains around the world, which severely impairs their growth and welfare. To explore the intrinsic factor causing crossed beaks, this study measured the length of bilateral mandibular ramus of affected birds, and investigated the genome-wide DNA methylation profiles of normal and affected sides of mandibular condyle. Results showed that the trait was caused by impaired development of unilateral mandibular ramus, which is extended through calcification of mandibular condyle. The methylation levels in the CG contexts were higher than that of CHG and CHH, with the highest methylation level of gene body region, followed by transcription termination sites and downstream. Subsequently, we identified 1,568 differentially methylated regions and 1,317 differentially methylated genes in CG contexts. Functional annotation analysis of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes showed that these genes were involved in bone mineralization and bone morphogenesis. Furthermore, by combining the WGBS and previous RNA-Seq data, 11 overlapped genes were regulated by both long non-coding RNA and DNA methylation. Among them, FIGNL1 is an important gene in calcification of mandibular condyle. Generally, because the affected genes play key roles in maintaining mandibular calcification, these changes may be pivotal factors of crossed beaks.

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Section: Discussionmentioning

confidence: 99%

Analysis of DNA Methylation Profiles in Mandibular Condyle of Chicks With Crossed Beaks Using Whole-Genome Bisulfite Sequencing

Shi

Bai

et al. 2021

Front. Genet.

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“…ONFH is a kind of pathological process, which often arises topical poor blood flow in the femoral head resulted from multiple complex causes, following with abnormal differentiation, imbalance of proportion and even death of active components in bone tissues such as osteoblasts, osteoclasts, bone marrow hematopoietic cells and subsequent repair abnormalities, resulting in further ischemia, necrosis, bone trabecular fracture and collapse of the femoral head (Mont et al, 2006;Zuo et al, 2016;Glueck et al, 2005;Hirata et al, 2007;Jones et al, 2003). Among them, steroidinduced ONFH (SINFH) is increasing year by year at clinical (Zhang et al, 2013;Yu et al, 2019), because of its unclear pathogenesis and lack of effective treatment (Wu et al, 2019), SINFH has become the focus of research in recent years. Therefore, in our study, we will explore the pathogenesis of SINFH to look for novel diagnostic and therapeutic targets.…”

Section: Sirna-gins2 Led To a Down-regulation Of Gins2 Expression And Up-regulated Expressions Of P53 And Gadd45a In Osteoblasts And Ostementioning

confidence: 99%

“…Among them, steroid-induced ONFH (SINFH), as an iatrogenic disease, the incidence of which is increasing with the years and usually develops at an early phase in the procedure of steroid administration (Zhang et al, 2013;Yu et al, 2019). The pathogenesis of ONFH is still misty, and the highly effective treatment for it is not appeared by now (Rajpura et al, 2011;Wu et al, 2019). Moreover, the treatment methods of SINFH at clinical are mainly marrow core decompression bone grafting, intervention, traditional Chinese medicine, bone marrow stem cell transplantation, artificial hip replacement and so on, but the fundamental prevention and treatment strategy of SINFH is lacking.…”

Section: Introductionmentioning

confidence: 99%

GINS2 affects activity/differentiation, apoptosis and proliferation of osteoblast and osteoclast in steroid-induced osteonecrosis of the femoral head by regulating P53/GADD45A signaling pathway

Tian

Wang

et al. 2022

Food Sci. Technol

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To investigate the function and mechanism of GINS complex subunit 2 (GINS2) in osteoblast and osteoclast in steroidinduced osteonecrosis of the femoral head (SINFH). Clinical specimens were collected from 40 cases of SINFH patients and 40 cases of control patients. Then, SINFH mouse model was built. Immediately, osteoblasts and osteoclasts were induced and differented from the pre-osteoblast cell line MC3T3-E1 and the mononuclear macrophage cell line RAW264.7 of mice, respectively. The qRT-PCR assay was used for detecting the expressions of GINS2, p53 and growth arrest and DNA damage 45A (GADD45A). The cytoactive, proliferation and apoptosis of osteoblasts and osteoclasts of SINFH mice were measured by tartaric acid phosphatase staining, CCK-8 and Annexin V-FITC/PI dual staining, respectively. GINS2 was up-regulated while p53/GADD45A was down-regulated in femoral tissues in SINFH patients and mice. GINS2 was down-regulated while p53 and GADD45A were up-regulated in osteoblasts of SINFH mice, which presented opposite trends in osteoclasts formations. GINS2 decreased osteoblasts activities and increased osteoclasts activities, inhibited apoptosis and promoted proliferation in osteoblasts and osteoclasts via p53/GADD45A pathway. GINS2 affects activity/differentiation, apoptosis and proliferation of osteoblast and osteoclast in steroid-induced osteonecrosis of the femoral head by regulating p53/GADD45A signaling pathway.

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“…Among epigenetics, DNA methylation is undoubtedly one of the most important fields. Studies have shown that DNA methylation plays a role in the occurrence and development of ONFH [ 7 – 9 ]. However, none of these alone can fully explain its underlying mechanism.…”

Section: Introductionmentioning

confidence: 99%

DNA methylation in the OPG/RANK/RANKL pathway is associated with steroid-induced osteonecrosis of the femoral head

Sun

Cao

Yang

et al. 2021

BMC Musculoskelet Disord

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Background Dysregulation of the OPG/RANK/RANKL signalling pathway is a key step in the occurrence of steroid-induced osteonecrosis of the femoral head (ONFH). This study aims to understand the degree of methylation of the OPG, RANK, and RANKL genes in steroid-related ONFH. Methods A case-control study was designed, including 50 patients (25 males and 25 females) and 50 matched controls. The European Molecular Biology Open Software Suite (EMBOSS) was used to predict the existence and location of CpG islands in the OPG, RANK, and RANKL genes. The Agena MassARRAY platform was used to detect the methylation status of the above genes in the blood of subjects. The relationship between the methylation level of CpG sites in each gene and steroid-related ONFH was analysed by the chi-square test, logistic regression analysis, and other statistical methods. Results In the CpG islands of the OPG, RANK, and RANKL genes in patients with steroid-related ONFH, several CpG sites with high methylation rates and high methylation levels were found. Some hypermethylated CpG sites increase the risk of steroid-related ONFH. In addition, a few hypermethylated CpG sites have predictive value for the early diagnosis of steroid-related ONFH. Conclusion Methylation of certain sites in the OPG/RANK/RANKL signalling pathway increases the risk of steroid-related ONFH. Some hypermethylated CpG sites may be used as early prediction and diagnostic targets for steroid-related ONFH.

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Genome-wide DNA methylation profiling of hip articular cartilage identifies differentially methylated loci associated with osteonecrosis of the femoral head

Cited by 12 publications

References 43 publications

Analysis of DNA Methylation Profiles in Mandibular Condyle of Chicks With Crossed Beaks Using Whole-Genome Bisulfite Sequencing

Analysis of DNA Methylation Profiles in Mandibular Condyle of Chicks With Crossed Beaks Using Whole-Genome Bisulfite Sequencing

GINS2 affects activity/differentiation, apoptosis and proliferation of osteoblast and osteoclast in steroid-induced osteonecrosis of the femoral head by regulating P53/GADD45A signaling pathway

DNA methylation in the OPG/RANK/RANKL pathway is associated with steroid-induced osteonecrosis of the femoral head

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