ArticleThe Journal of biological chemistry2019
Hyaluronan synthase 2 (HAS2) overexpression diminishes the procatabolic activity of chondrocytes by a mechanism independent of extracellular hyaluronan.
Article in The Journal of biological chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 22 citations in OpenAlex.
- Cartilage-SpecificBiomedicines · 2026Article
- Structure and Function of the Extracellular Matrix in Normal and Pathological Conditions: Looking at the Bicuspid Aortic Valve.International journal of molecular sciences · 2025Review
- Molecular Adaptations to Repeated Radiation Exposure in Triple-Negative Breast Cancer: Dysregulation of Cell Adhesion, Mitochondrial Function, and Epithelial-Mesenchymal Transition.International journal of molecular sciences · 2025Article
- Potential therapeutic targets for pelvic organ prolapse: insights from key genes related to blood vessel development.Frontiers in medicine · 2024Article
- Modulation of lncRNA links endothelial glycocalyx to vascular dysfunction of tyrosine kinase inhibitor.Cardiovascular research · 2023Article
- Development of Therapeutic Agent for Osteoarthritis via Inhibition of KIAA1199 Activity: Effect of Ipriflavone In Vivo.International journal of molecular sciences · 2023Article
- Downregulation of HAS‑2 regulates the chondrocyte cytoskeleton and induces cartilage degeneration by activating the RhoA/ROCK signaling pathway.International journal of molecular medicine · 2023Article
- Xeno-free cultured mesenchymal stromal cells release extracellular vesicles with a "therapeutic" miRNA cargo ameliorating cartilage inflammationTheranostics · 2023Article
- 3'UTR shortening of HAS2 promotes hyaluronan hyper-synthesis and bioenergetic dysfunction in pulmonary hypertension.Matrix biology : journal of the International Society for Matrix Biology · 2022Article
- Crosstalk between CD4 T cells and synovial fibroblasts from human arthritic joints promotes hyaluronan-dependent leukocyte adhesion and inflammatory cytokine expression in vitro.Matrix biology plus · 2022Article
- Drug delivery systems for treatment of temporomandibular joint osteoarthritis.Frontiers in pharmacology · 2022Review
- Synaptic Hyaluronan Synthesis and CD44-Mediated Signaling Coordinate Neural Circuit Development.Cells · 2021Article
- Metabolic reprogramming in chondrocytes to promote mitochondrial respiration reduces downstream features of osteoarthritis.Scientific reports · 2021Article
- Augmented Chondroitin Sulfate Proteoglycan Has Therapeutic Potential for Intervertebral Disc Degeneration by Stimulating Anabolic Turnover in Bovine Nucleus Pulposus Cells under Changes in Hydrostatic Pressure.International journal of molecular sciences · 2021Article
- Hyaluronan regulates synapse formation and function in developing neural networks.Scientific reports · 2020Article
- Suppression of murine osteoarthritis by 4-methylumbelliferone.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2020Article
- Chondroprotective effects of 4-methylumbelliferone and hyaluronan synthase-2 overexpression involve changes in chondrocyte energy metabolism.The Journal of biological chemistry · 2019Article
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Authors and funding
8 authors at 1 institution in 2 countries.
Funding
Abstract
Osteoarthritis (OA) is a progressive degenerative disease of the joints caused in part by a change in the phenotype of resident chondrocytes within affected joints. This altered phenotype, often termed proinflammatory or procatabolic, features enhanced production of endoproteinases and matrix metallo-proteinases (MMPs) as well as secretion of endogenous inflammatory mediators. Degradation and reduced retention of the proteoglycan aggrecan is an early event in OA. Enhanced turnover of hyaluronan (HA) is closely associated with changes in aggrecan. Here, to determine whether experimentally increased HA production promotes aggrecan retention and generates a positive feedback response, we overexpressed HA synthase-2 (HAS2) in chondrocytes via an inducible adenovirus construct (HA synthase-2 viral overexpression; HAS2-OE). HAS2-OE incrementally increased high-molecular-mass HA >100-fold within the cell-associated and growth medium pools. More importantly, our results indicated that the HAS2-OE expression system inhibits MMP3, MMP13, and other markers of the procatabolic phenotype (such as TNF-stimulated gene 6 protein (TSG6)) and also enhances aggrecan retention. These markers were inhibited in OA-associated chondrocytes and in chondrocytes activated by interleukin-1β (IL1β), but also chondrocytes activated by lipopolysaccharide (LPS), tumor necrosis factor α (TNFα), or HA oligosaccharides. However, the enhanced extracellular HA resulting from HAS2-OE did not reduce the procatabolic phenotype of neighboring nontransduced chondrocytes as we had expected. Rather, HA-mediated inhibition of the phenotype occurred only in transduced cells. In addition, high HA biosynthesis rates, especially in transduced procatabolic chondrocytes, resulted in marked changes in chondrocyte dependence on glycolysis
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