ArticleNature communications2019
Tankyrase inhibition preserves osteoarthritic cartilage by coordinating cartilage matrix anabolism via effects on SOX9 PARylation.
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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34 citing papers in PubMed, 50 citations in OpenAlex.
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- Research progress and prospects of exosomes from diverse cellular sources in the treatment of knee osteoarthritis: a narrative review.Frontiers in surgery · 2026Review
- Therapeutic potential of SOX family transcription factors in osteoarthritis.Annals of medicine · 2025Review
- Development of an iPSC-based screening platform identifying enhancers of chondrogenesis.Osteoarthritis and cartilage open · 2025Article
- Cartilage-protective effects of lopinavir/ritonavir: in vitro and in silico exploration of the HIF-1α/SOX9/IL-1β pathway.Journal of orthopaedic surgery and research · 2025Article
- Blockade of ZMIZ1-GATA4 Axis Regulation Restores Youthfulness to Aged Cartilage.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Targeting the PARylation-Dependent Ubiquitination Signaling Pathway for Cancer Therapies.Biomolecules · 2025Review
- Regulation of senescence-associated secretory phenotypes in osteoarthritis by cytosolic UDP-GlcNAc retention and O-GlcNAcylation.Nature communications · 2025Article
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- SASH1 S519N Variant Links Skin Hyperpigmentation and Premature Hair Graying to Dysfunction of Melanocyte Lineage.The Journal of investigative dermatology · 2025Article
- Identification and analysis of immune aging related biomarkers in cartilage and meniscus tissues of osteoarthritis.American journal of clinical and experimental immunology · 2025Article
- SOX9: a key transcriptional regulator in organ fibrosis.Frontiers in pharmacology · 2025Review
- A multifunctional nanogel encapsulating layered double hydroxide for enhanced osteoarthritis treatment via protection of chondrocytes and ECM.Materials today. Bio · 2024Article
- Inhibitory Effect of a Tankyrase Inhibitor on Mechanical Stress-Induced Protease Expression in Human Articular Chondrocytes.International journal of molecular sciences · 2024Article
- Research progress of ultrasound in accurate evaluation of cartilage injury in osteoarthritis.Frontiers in endocrinology · 2024Review
- Identification of ZNF652 as a Diagnostic and Therapeutic Target in Osteoarthritis Using Machine Learning.Journal of inflammation research · 2024Article
- Chondroprotective effects ofFood science & nutrition · 2023Article
- Tankyrase: a promising therapeutic target with pleiotropic action.Naunyn-Schmiedeberg's archives of pharmacology · 2023Review
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Authors and funding
14 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Osteoarthritis (OA) is a prevalent degenerative disease, which involves progressive and irreversible destruction of cartilage matrix. Despite efforts to reconstruct cartilage matrix in osteoarthritic joints, it has been a difficult task as adult cartilage exhibits marginal repair capacity. Here we report the identification of tankyrase as a regulator of the cartilage anabolism axis based on systems-level factor analysis of mouse reference populations. Tankyrase inhibition drives the expression of a cartilage-signature matrisome and elicits a transcriptomic pattern that is inversely correlated with OA progression. Furthermore, tankyrase inhibitors ameliorate surgically induced OA in mice, and stem cell transplantation coupled with tankyrase knockdown results in superior regeneration of cartilage lesions. Mechanistically, the pro-regenerative features of tankyrase inhibition are mainly triggered by uncoupling SOX9 from a poly(ADP-ribosyl)ation (PARylation)-dependent protein degradation pathway. Our findings provide insights into the development of future OA therapies aimed at reconstruction of articular cartilage.
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