ArticleScientific reports2017
Glycogen Synthase Kinase-3β Inhibition Links Mitochondrial Dysfunction, Extracellular Matrix Remodelling and Terminal Differentiation in Chondrocytes.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
21 citing papers in PubMed, 41 citations in OpenAlex.
- Dysregulation of the glycolysis-mitochondrial metabolism axis in osteoarthritis: mechanisms and therapeutic implications.Journal of orthopaedic translation · 2026Review
- Histone Deacetylase 6 Controls Atrial Fibrosis and Remodeling in Postinfarction Mice Through the Modulation of Wnt3a/GSK-3β Signaling.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- The Effect of Nerve Growth Factor on Cartilage Fibrosis and Hypertrophy duringInternational journal of stem cells · 2025Article
- Recent development of mitochondrial metabolism and dysfunction in osteoarthritis.Frontiers in pharmacology · 2025Review
- Association of thyroid hormone with osteoarthritis: from mendelian randomization and RNA sequencing analysis.Journal of orthopaedic surgery and research · 2024Article
- The role and intervention of mitochondrial metabolism in osteoarthritis.Molecular and cellular biochemistry · 2024Review
- Mitochondrial heterogeneity and adaptations to cellular needs.Nature cell biology · 2024Review
- Stem Cell-Based or Cell-Free Gene Therapy in Chondrocyte Regeneration: Synovial Fluid-Derived Mesenchymal Stem Cell Exosomes.Current molecular medicine · 2024Article
- Epidermal-dermal coupled spheroids are important for tissue pattern regeneration in reconstituted skin explant cultures.NPJ Regenerative medicine · 2023Article
- Cytocompatibility and Osteoinductive Properties of Collagen-Fibronectin Hydrogel Impregnated with siRNA Targeting Glycogen Synthase Kinase 3β: In Vitro Study.Biomedicines · 2023Article
- Progranulin Protects against Hyperglycemia-Induced Neuronal Dysfunction through GSK3β Signaling.Cells · 2023Article
- Loss of PRDX6 Aborts Proliferative and Migratory Signaling in Hepatocarcinoma Cell Lines.Antioxidants (Basel, Switzerland) · 2023Article
- Glycogen synthesis and beyond, a comprehensive review of GSK3 as a key regulator of metabolic pathways and a therapeutic target for treating metabolic diseases.Medicinal research reviews · 2022Review
- Glycogen Synthase Kinase 3Stem cells international · 2022Article
- Loss of Autophagy Causes Increased Apoptosis of Tibial Plateau Chondrocytes in Guinea Pigs with Spontaneous Osteoarthritis.Cartilage · 2021Article
- Pleiotropic Roles of NOTCH1 Signaling in the Loss of Maturational Arrest of Human Osteoarthritic Chondrocytes.International journal of molecular sciences · 2021Article
- Effects of Visfatin on Intracellular Mechanics and Catabolism in Human Primary Chondrocytes through Glycogen Synthase Kinase 3β Inactivation.International journal of molecular sciences · 2021Article
- Glycogen synthase kinase 3 alpha/beta deletion induces precocious growth plate remodeling in mice.Journal of molecular medicine (Berlin, Germany) · 2021Article
- Polyamine supplementation reduces DNA damage in adipose stem cells cultured in 3-D.Scientific reports · 2019Article
- Chondrocyte-Specific RUNX2 Overexpression Accelerates Post-traumatic Osteoarthritis Progression in Adult Mice.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2019Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Following inflammatory stimuli, GSK3 inhibition functions as a hub with pleiotropic effects leading to cartilage degradation. However, little is known about the effects triggered by its direct inhibition as well as the effects on mitochondrial pathology, that contributes to osteoarthritis pathogenesis. To this aim we assessed the molecular mechanisms triggered by GSK3β inactivating stimuli on 3-D (micromass) cultures of human articular chondrocytes. Stimuli were delivered either at micromass seeding (long term) or after maturation (short term) to explore "late" effects on terminal differentiation or "early" mitochondrial effects, respectively. GSK3β inhibition significantly enhanced mitochondrial oxidative stress and damage and endochondral ossification based on increased nuclear translocation of Runx-2 and β-catenin, calcium deposition, cell death and enhanced remodelling of the extracellular matrix as demonstrated by the increased collagenolytic activity of supernatants, despite unmodified (MMP-1) or even reduced (MMP-13) collagenase gene/protein expression. Molecular dissection of the underlying mechanisms showed that GSK3β inhibition achieved with pharmacological/silencing strategies impacted on the control of collagenolytic activity, via both decreased inhibition (reduced TIMP-3) and increased activation (increased MMP-10 and MMP-14). To conclude, the inhibition of GSK3β enhances terminal differentiation via concerted effects on ECM and therefore its activity represents a tool to keep articular cartilage homeostasis.
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