YTHDF2-dependent m⁶A modification of FOXO3 mRNA mediates TIMP1 expression and contributes to intervertebral disc degeneration following ROS stimulation.

ABSTRACT: The accumulation of reactive oxygen species (ROS) significantly contributes to intervertebral disc degeneration (IDD), but the mechanisms behind this phenomenon remain unclear. This study revealed elevated ROS levels in the intervertebral discs (IVDs) of aged mice compared to those of younger mice. The local application of hydrogen peroxide (H₂O₂) near lumbar discs also induced ROS accumulation and IDD. Isobaric tags for relative and absolute quantitation (iTRAQ) analysis of discs from aged and H₂O₂-injected mice showed increased levels of YTH N6-methyladenosine RNA binding protein F2 (YTHDF2) and matrix metallopeptidase 1/3/7/9 (MMP1/3/7/9), along with decreased levels of forkhead box O3 (FOXO3) and TIMP1 (tissue inhibitor of metalloproteinases

SUBMITTER: Wang F 

PROVIDER: S-EPMC11615171 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature