Dysregulation of the NUDT7-PGAM1 axis is responsible for chondrocyte death during osteoarthritis pathogenesis

Nature Communications
Jinsoo SongEun-Jung Jin

Abstract

Osteoarthritis (OA) is the most common degenerative joint disease; however, its etiopathogenesis is not completely understood. Here we show a role for NUDT7 in OA pathogenesis. Knockdown of NUDT7 in normal human chondrocytes results in the disruption of lipid homeostasis. Moreover, Nudt7-/- mice display significant accumulation of lipids via peroxisomal dysfunction, upregulation of IL-1β expression, and stimulation of apoptotic death of chondrocytes. Our genome-wide analysis reveals that NUDT7 knockout affects the glycolytic pathway, and we identify Pgam1 as a significantly altered gene. Consistent with the results obtained on the suppression of NUDT7, overexpression of PGAM1 in chondrocytes induces the accumulation of lipids, upregulation of IL-1β expression, and apoptotic cell death. Furthermore, these negative actions of PGAM1 in maintaining cartilage homeostasis are reversed by the co-introduction of NUDT7. Our results suggest that NUDT7 could be a potential therapeutic target for controlling cartilage-degrading disorders.

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Citations

Mar 9, 2019·Journal of Lipid Research·Stephanie A ShumarRoberta Leonardi
Mar 7, 2020·Cancers·Jinsoo SongEun-Jung Jin
Jun 5, 2019·Nature Communications·Sho MokudaHiroshi Asahara
Mar 21, 2020·The Journal of Gene Medicine·Shaojian ChenXiaguang Chen
Jul 12, 2019·Frontiers in Veterinary Science·Ramesh C GuptaAnita Sinha
May 1, 2019·Journal of Lipid Research·Stephanie A ShumarRoberta Leonardi
Apr 3, 2020·Progress in Lipid Research·Philippe NaquetRoberta Leonardi
Oct 15, 2020·International Journal of Molecular Sciences·Hyo Young JungIn Koo Hwang
Jul 31, 2021·Biochemical and Biophysical Research Communications·Hye-Kyoung OhDae-Won Kim

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Datasets Mentioned

BETA
MBS705127

Methods Mentioned

BETA
immunoprecipitation
acetylation
PCR
genotyping
dissection
biopsy
Protein Assay
Assay
ELISA

Software Mentioned

Ingenuity Pathway Analysis ( IPA )
Affymetrix GeneChipCommand Console
Ingenuity Pathway Analysis ( IPA
GSEA
PermutMatrix
cufflinks

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