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Updated: Feb 6, 2026
Standardized Histomorphometric Evaluation of Osteoarthritis in a Surgical Mouse Model
Published on: May 6, 2020
Dysregulation of the NUDT7-PGAM1 axis is responsible for chondrocyte death during osteoarthritis pathogenesis
Jinsoo Song1, In-Jeoung Baek2, Churl-Hong Chun3
1Department of Biological Sciences, College of Natural Sciences, Wonkwang University, Iksan, Chunbuk, 54538, Republic of Korea.
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.
Insights
NUDT7 disruption impairs lipid homeostasis and promotes chondrocyte apoptosis in osteoarthritis. Restoring NUDT7 may offer a therapeutic strategy for cartilage degeneration.
Area of Science:
- Biochemistry
- Molecular Biology
- Pathology
Background:
- Osteoarthritis (OA) is a prevalent degenerative joint disease with incompletely understood causes.
- Maintaining cartilage homeostasis is crucial for joint health and function.
Purpose of the Study:
- To investigate the role of NUDT7 in the pathogenesis of osteoarthritis.
- To elucidate the molecular mechanisms linking NUDT7 to cartilage degradation.
Main Methods:
- Knockdown of NUDT7 in human chondrocytes.
- Analysis of Nudt7 knockout mice.
- Genome-wide expression analysis.
- Overexpression of PGAM1 in chondrocytes.
Main Results:
- NUDT7 knockdown disrupted lipid homeostasis in chondrocytes.
- Nudt7 knockout mice exhibited lipid accumulation, peroxisomal dysfunction, IL-1β upregulation, and chondrocyte apoptosis.
- NUDT7 knockout affected the glycolytic pathway, altering Pgam1 expression.
- PGAM1 overexpression mimicked NUDT7 suppression effects, while NUDT7 co-introduction reversed them.
Conclusions:
- NUDT7 plays a critical role in maintaining cartilage homeostasis.
- Dysregulation of NUDT7 and its associated pathways contribute to osteoarthritis pathogenesis.
- NUDT7 represents a potential therapeutic target for osteoarthritis and other cartilage-degrading disorders.
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