ArticleMatrix biology : journal of the International Society for Matrix Biology2016
CRISPR/Cas9 knockout of HAS2 in rat chondrosarcoma chondrocytes demonstrates the requirement of hyaluronan for aggrecan retention.
Article in Matrix biology : journal of the International Society for Matrix Biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 34 citations in OpenAlex.
- Cartilage-SpecificBiomedicines · 2026Article
- Molecular signaling pathways in osteoarthritis and biomaterials for cartilage regeneration: a review.Bioengineered · 2025Review
- Mechanobiology of Hyaluronan: Connecting Biomechanics and Bioactivity in Musculoskeletal Tissues.Annual review of biomedical engineering · 2024Review
- Potential therapeutic strategies for osteoarthritis via CRISPR/Cas9 mediated gene editing.Reviews in endocrine & metabolic disorders · 2024Review
- Anti-Inflammatory Effects of the 35kDa Hyaluronic Acid Fragment (B-HA/HA35).Journal of inflammation research · 2023Article
- Prospective bacterial and fungal sources of hyaluronic acid: A review.Computational and structural biotechnology journal · 2022Review
- Harnessing Tissue-derived Extracellular Vesicles for Osteoarthritis Theranostics.Theranostics · 2022Review
- Synaptic Hyaluronan Synthesis and CD44-Mediated Signaling Coordinate Neural Circuit Development.Cells · 2021Article
- The Role of IGF/IGF-IR-Signaling and Extracellular Matrix Effectors in Bone Sarcoma Pathogenesis.Cancers · 2021Review
- Control of the Autophagy Pathway in Osteoarthritis: Key Regulators, Therapeutic Targets and Therapeutic Strategies.International journal of molecular sciences · 2021Review
- Angiostatic cues from the matrix: Endothelial cell autophagy meets hyaluronan biology.The Journal of biological chemistry · 2020Review
- Hyaluronan: Metabolism and Function.Biomolecules · 2020Review
- Hyaluronan regulates synapse formation and function in developing neural networks.Scientific reports · 2020Article
- Emerging Gene-Editing Modalities for Osteoarthritis.International journal of molecular sciences · 2020Review
- Chondroprotective effects of 4-methylumbelliferone and hyaluronan synthase-2 overexpression involve changes in chondrocyte energy metabolism.The Journal of biological chemistry · 2019Article
- Hyaluronan synthase 2 (HAS2) overexpression diminishes the procatabolic activity of chondrocytes by a mechanism independent of extracellular hyaluronan.The Journal of biological chemistry · 2019Article
- The pericellular hyaluronan of articular chondrocytes.Matrix biology : journal of the International Society for Matrix Biology · 2019Review
- Hyaluronan biology: A complex balancing act of structure, function, location and context.Matrix biology : journal of the International Society for Matrix Biology · 2019Review
- Simvastatin promotes restoration of chondrocyte morphology and phenotype.Archives of biochemistry and biophysics · 2019Article
- Cartilage diseases.Matrix biology : journal of the International Society for Matrix Biology · 2018Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Hyaluronan (HA) plays an essential role in cartilage where it functions to retain aggrecan. Previous studies have suggested that aggrecan is anchored indirectly to the plasma membrane of chondrocytes via its binding to cell-associated HA. However, reagents used to test these observations such as hyaluronidase and HA oligosaccharides are short term and may have side activities that complicate interpretation. Using the CRISPR/Cas9 gene editing approach, a model system was developed by generating HA-deficient chondrocyte cell lines. HA synthase-2 (Has2)-specific single guide RNA was introduced into two different variant lines of rat chondrosarcoma chondrocytes; knockout clones were isolated and characterized. Two other members of the HA synthase gene family were expressed at very low relative copy number but showed no compensatory response in the Has2 knockouts. Wild type chondrocytes of both variants exhibited large pericellular matrices or coats extending from the plasma membrane. Addition of purified aggrecan monomer expanded the size of these coats as the proteoglycan became retained within the pericellular matrix. Has2 knockout chondrocytes lost all capacity to assemble a particle-excluding pericellular matrix and more importantly, no matrices formed around the knockout cells following the addition of purified aggrecan. When grown as pellet cultures so as to generate a bioengineered neocartilage tissue, the Has2 knockout chondrocytes assumed a tightly-compacted morphology as compared to the wild type cells. When knockout chondrocytes were transduced with Adeno-ZsGreen1-mycHas2, the cell-associated pericellular matrices were restored including the capacity to bind and incorporate additional exogenous aggrecan into the matrix. These results suggest that HA is essential for aggrecan retention and maintaining cell separation during tissue formation.
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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 Socratic graph.