Genomics

Dataset Information

52

DNA methyltransferase 3b regulates articular cartilage homeostasis by altering chondrocyte metabolism


ABSTRACT: Osteoarthritis (OA) is the most common form of arthritis worldwide. It is a complex disease affecting the whole joint but is generally characterized by progressive degradation of articular cartilage. Recent genome-wide association screens have implicated distinct DNA methylation signatures in OA patients. We show that the de novo DNA methyltransferase (Dnmt) 3b, but not Dnmt3a, is present in healthy murine and human articular chondrocytes and expression decreases in OA mouse models and in chondrocytes from human OA patients. Targeted deletion of Dnmt3b in murine articular chondrocytes results in an early onset and progressive post-natal OA-like pathology. RNA-seq and MethylC-seq analyses of Dnmt3b loss-of-function chondrocytes shows that cellular metabolic processes are affected. Specifically, TCA metabolites and mitochondrial respiration are elevated. Importantly, a chondroprotective effect was found following Dnmt3b gain-of-function in murine articular chondrocytes in vitro and in vivo. This study shows that Dnmt3b plays a significant role in regulating post-natal articular cartilage homeostasis. Cellular pathways regulated by Dnmt3b in chondrocytes may provide novel targets for therapeutic approaches to treat OA. Overall design: RNA-seq and whole-genome bisulfite sequencing (WGBS) of DNMT3b knockout and control samples in mouse.

INSTRUMENT(S): Illumina HiSeq 2500 (Mus musculus)

ORGANISM(S): Mus Musculus

SUBMITTER: Daofeng Li  

PROVIDER: GSE85148 | GEO | 2017-07-24

SECONDARY ACCESSION(S): PRJNA336344

REPOSITORIES: GEO

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Publications

DNA methyltransferase 3b regulates articular cartilage homeostasis by altering metabolism.

Shen Jie J   Wang Cuicui C   Li Daofeng D   Xu Taotao T   Myers Jason J   Ashton John M JM   Wang Ting T   Zuscik Michael J MJ   McAlinden Audrey A   O'Keefe Regis J RJ  

JCI insight 20170615 12


Osteoarthritis (OA) is the most common form of arthritis worldwide. It is a complex disease affecting the whole joint but is generally characterized by progressive degradation of articular cartilage. Recent genome-wide association screens have implicated distinct DNA methylation signatures in OA patients. We show that the de novo DNA methyltransferase (Dnmt) 3b, but not Dnmt3a, is present in healthy murine and human articular chondrocytes and its expression decreases in OA mouse models and in ch  ...[more]

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