ArticleAging cell2020
Liver osteopontin is required to prevent the progression of age-related nonalcoholic fatty liver disease.
Article in Aging cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 32 citations in OpenAlex.
- The contested association between MASLD and osteoporosis: a narrative review of heterogeneous evidence and modifying factors.Archives of osteoporosis · 2026Review
- Article
- Stem cell-based therapeutic strategies for liver aging.Liver research (Beijing, China) · 2025Review
- Determinants of abnormal liver-related biomarkers in adult COVID-19 patients.Frontiers in cellular and infection microbiology · 2025Article
- Serum LCAT as a Gender-Neutral Biomarker for Early Osteoporosis: A Multicenter Cohort Validation Study.International journal of general medicine · 2025Article
- Heat shock proteins (HSPs) in non-alcoholic fatty liver disease (NAFLD): from molecular mechanisms to therapeutic avenues.Biomarker research · 2024Review
- Neddylation inhibition prevents acetaminophen-induced liver damage by enhancing the anabolic cardiolipin pathway.Cell reports. Medicine · 2024Article
- Involvement of Matricellular Proteins in Cellular Senescence: Potential Therapeutic Targets for Age-Related Diseases.International journal of molecular sciences · 2024Review
- Osteopontin Rejuvenates Senescent Adipose-Derived Stem Cells and Restores their Bone Tissue Regenerative Function.Stem cell reviews and reports · 2024Article
- A biomarker framework for liver aging: the Aging Biomarker Consortium consensus statement.Life medicine · 2024Article
- Anti-osteoporotic treatments in the era of non-alcoholic fatty liver disease: friend or foe.Frontiers in endocrinology · 2024Review
- Non-Alcoholic Fatty Liver Disease and Bone Tissue Metabolism: Current Findings and Future Perspectives.International journal of molecular sciences · 2023Review
- Biomarkers of aging.Science China. Life sciences · 2023Review
- Osteopontin Promotes Macrophage M1 Polarization by Activation of the JAK1/STAT1/HMGB1 Signaling Pathway in Nonalcoholic Fatty Liver Disease.Journal of clinical and translational hepatology · 2023Article
- Lactoferrin, Osteopontin and Lactoferrin-Osteopontin Complex: A Critical Look on Their Role in Perinatal Period and Cardiometabolic Disorders.Nutrients · 2023Review
- The complexity of p53-mediated metabolic regulation in tumor suppression.Seminars in cancer biology · 2022Review
- Article
- Modulation of Oxidative Stress-Induced Senescence during Non-Alcoholic Fatty Liver Disease.Antioxidants (Basel, Switzerland) · 2022Review
- The Role of Osteopontin in Tumor Progression Through Tumor-Associated Macrophages.Frontiers in oncology · 2022Review
- Osteopontin Takes Center Stage in Chronic Liver Disease.Hepatology (Baltimore, Md.) · 2021Review
Corrections and comments
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Authors and funding
20 authors at 6 institutions in 2 countries.
Funding
Abstract
Osteopontin (OPN), a senescence-associated secretory phenotype factor, is increased in patients with nonalcoholic fatty liver disease (NAFLD). Cellular senescence has been associated with age-dependent hepatosteatosis. Thus, we investigated the role of OPN in the age-related hepatosteatosis. For this, human serum samples, animal models of aging, and cell lines in which senescence was induced were used. Metabolic fluxes, lipid, and protein concentration were determined. Among individuals with a normal liver, we observed a positive correlation between serum OPN levels and increasing age. This correlation with age, however, was absent in patients with NAFLD. In wild-type (WT) mice, serum and liver OPN were increased at 10 months old (m) along with liver p53 levels and remained elevated at 20m. Markers of liver senescence increased in association with synthesis and concentration of triglycerides (TG) in 10m OPN-deficient (KO) hepatocytes when compared to WT hepatocytes. These changes in senescence and lipid metabolism in 10m OPN-KO mice liver were associated with the decrease of 78 kDa glucose-regulated protein (GRP78), induction of ER stress, and the increase in fatty acid synthase and CD36 levels. OPN deficiency in senescent cells also diminished GRP78, the accumulation of intracellular TG, and the increase in CD36 levels. In 20m mice, OPN loss led to increased liver fibrosis. Finally, we showed that OPN expression in vitro and in vivo was regulated by p53. In conclusion, OPN deficiency leads to earlier cellular senescence, ER stress, and TG accumulation during aging. The p53-OPN axis is required to inhibit the onset of age-related hepatosteatosis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.