ArticleEBioMedicine2019
Fibrates as drugs with senolytic and autophagic activity for osteoarthritis therapy.
Article in EBioMedicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers.
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Who cites it
99 citing papers in PubMed, 144 citations in OpenAlex.
- The ageing immune system as a driver of systemic ageing.Nature reviews. Immunology · 2026Review
- Exploring mitochondrial functions and dysfunctions in chondrocytes: toward the identification of novel therapies for osteoarthritis.Bone research · 2026Review
- Insights into the therapeutic strategies for aging and aging-associated diseases.Signal transduction and targeted therapy · 2026Review
- The Aging Microenvironment Shapes Angiogenic Remodeling in IBD-Associated Colorectal Carcinogenesis.Aging cell · 2026Review
- Research progress on cellular senescence in the pathogenesis and treatment of osteoarthritis and temporomandibular joint osteoarthritis.Journal of oral & facial pain and headache · 2026Review
- Neuroendocrine-associated epigenetic factors in cellular senescence: mechanisms and therapeutic implications.Biogerontology · 2026Review
- Chondrocyte Senescence in Osteoarthritis: Potential Targets and Pharmacological Interventions.Cartilage · 2026Article
- Review
- Cleaning, Chasing and Calming: Promising Paradigms of Senotherapy in Aging-Related Diseases.International journal of biological sciences · 2026Review
- Senescent fibroblasts in aging and pulmonary fibrosis.Frontiers in aging · 2026Review
- Inflammaging and Senescence-Associated Secretory Phenotype (SASP) in Psoriasis - A Narrative Review of Potential Mechanisms and Anti-Inflammaging Strategies.Psoriasis (Auckland, N.Z.) · 2026Review
- Aging microenvironment in osteoarthritis focusing on early-stage alterations and targeted therapies.Bone research · 2025Review
- The Senotherapeutic Effects of APPA (Apocynin [AP] and Paeonol [PA]) on Senescent Human Chondrocytes.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Cold exposure promotes the progression of osteoarthritis through downregulating APOE in cartilage.EMBO molecular medicine · 2025Article
- Neutralization of acyl CoA binding protein (ACBP) for the experimental treatment of osteoarthritis.Cell death and differentiation · 2025Article
- Senotherapy for chronic lung disease.Pharmacological reviews · 2025Review
- Development and Application of a Senolytic Predictor for Discovery of Novel Senolytic Compounds and Herbs.Molecules (Basel, Switzerland) · 2025Article
- The crucial function of IDO1 in pulmonary fibrosis: From the perspective of mitochondrial fusion in lung fibroblasts and targeted molecular inhibition.Acta pharmaceutica Sinica. B · 2025Article
- Extracellular vesicles in age-related diseases: disease pathogenesis, intervention, and biomarker.Stem cell research & therapy · 2025Review
- Anti-senescence therapies: a new concept to address cardiovascular disease.Cardiovascular research · 2025Review
39 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 6 institutions in 4 countries.
Funding
Abstract
backgroundAgeing-related failure of homeostasis mechanisms contributes to articular cartilage degeneration and osteoarthritis (OA), for which disease-modifying treatments are not available. Our objective was to identify molecules to prevent OA by regulating chondrocyte senescence and autophagy.
methodsHuman chondrocytes with IL-6 induced senescence and autophagy suppression and SA-β-gal as a reporter of senescence and LC3 as reporter of autophagic flux were used to screen the Prestwick Chemical Library of approved drugs. Preclinical cellular, tissue and blood from OA and blood from OA and ageing models were used to test the efficacy and relevance of activating PPARα related to cartilage degeneration.
findingsSenotherapeutic molecules with pro-autophagic activity were identified. Fenofibrate (FN), a PPARα agonist used for dyslipidaemias in humans, reduced the number of senescent cells via apoptosis, increased autophagic flux, and protected against cartilage degradation. FN reduced both senescence and inflammation and increased autophagy in both ageing human and OA chondrocytes whereas PPARα knockdown conferred the opposite effect. Moreover, PPARα expression was reduced through both ageing and OA in mice and also in blood and cartilage from knees of OA patients. Remarkably, in a retrospective study, fibrate treatment improved OA clinical conditions in human patients from the Osteoarthritis Initiative (OAI) Cohort.
interpretationThese results demonstrate that FDA-approved fibrate drugs targeting lipid metabolism protect against cartilage degeneration seen with ageing and OA. Thus, these drugs could have immediate clinically utility for age-related cartilage degeneration and OA treatment. FUND: This study was supported by Instituto de Salud Carlos III- Ministerio de Ciencia, Innovación y Universidades, Spain, Plan Estatal 2013-2016 and Fondo Europeo de Desarrollo Regional (FEDER), "Una manera de hacer Europa", PI14/01324 and PI17/02059, by Innopharma Pharmacogenomics platform applied to the validation of targets and discovery of drugs candidates to preclinical phases, Ministerio de Economía y Competitividad, by grants of the National Instiutes of Health to PDR (P01 AG043376 and U19 AG056278). We thank FOREUM Foundation for Research in Rheumatology for their support.
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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.