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Metadata

Name
Role of TET1 Mediated 5hmC in Osteoarthritis [RNA-seq]
Repository
Gene Expression Omnibus
Identifier
geo.series:GSE143447
Description
No disease-modifying drugs exist to treat osteoarthritis (OA), a degenerative disease of the joint.  The complexity of OA necessitates a combinational and broad therapeutic approach. Epigenetic regulators are able to control large programs of genes, and recent work from our group and others have showcased systemic epigenetic dysregulation in OA. Previously, we demonstrated that OA chondrocytes accumulate 5-fold more 5-hydroxymethylcytosine (5hmC), an oxidized derivative of methylcytosine (5mC) associated with gene activation, at disease relevant sites. To test if 5hmC has a role in the early onset of OA, we utilized a mouse model of surgically induced OA, destabilization of the medial meniscus (DMM), and found that DMM mice gained ~40,000 differentially hydroxymethylated sites. Genetic loss of TET1, the enzyme responsible for 5hmC deposition, prevented pathologic gain of 5hmC, activation of many OA pathways, and protected mice from OA development. To test the clinical potential of a TET1 based OA therapy, we injected 2-hydroxyglutarate (2-HG), a TET inhibitor, into the joint after DMM induction and  observed stalled disease progression. Collectively, these data show that TET1 mediated 5hmC deposition regulates multiple OA pathways and that its modulation can be a powerful clinical tool for OA.
Data or Study Types
Expression profiling by high throughput sequencing
Source Organization
National Center for Biotechnology Information
Access Conditions
available
Year
2020
Access Hyperlink
http://www.ncbi.nlm.nih.gov/sites/GDSbrowser?acc=GSE143447

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