ArticleArthritis and rheumatism2012
Mechanisms involved in enhancement of the expression and function of aggrecanases by hyaluronan oligosaccharides.
Article in Arthritis and rheumatism, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 27 citations in OpenAlex.
- Modulation of lncRNA links endothelial glycocalyx to vascular dysfunction of tyrosine kinase inhibitor.Cardiovascular research · 2023Article
- Prospective bacterial and fungal sources of hyaluronic acid: A review.Computational and structural biotechnology journal · 2022Review
- Role of Hyaluronan in Inflammatory Effects on Human Articular Chondrocytes.Inflammation · 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 role of increased synovial fluid A disintegrin and metalloproteinase with thrombospondin motifs4 and serglycin levels in osteoarthritis.Irish journal of medical science · 2019Article
- The pericellular hyaluronan of articular chondrocytes.Matrix biology : journal of the International Society for Matrix Biology · 2019Review
- Hyaluronan in the experimental injury of the cartilage: biochemical action and protective effects.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2018Review
- Development of a thermosensitive HAMA-containing bio-ink for the fabrication of composite cartilage repair constructs.Biofabrication · 2017Article
- CRISPR/Cas9 knockout of HAS2 in rat chondrosarcoma chondrocytes demonstrates the requirement of hyaluronan for aggrecan retention.Matrix biology : journal of the International Society for Matrix Biology · 2016Article
- 4-Methylumbelliferone Diminishes Catabolically Activated Articular Chondrocytes and Cartilage Explants via a Mechanism Independent of Hyaluronan Inhibition.The Journal of biological chemistry · 2016Article
- Effect of osteopontin on the mRNA expression of ADAMTS4 and ADAMTS5 in chondrocytes from patients with knee osteoarthritis.Experimental and therapeutic medicine · 2015Article
- Chopping off the chondrocyte proteome.Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals · 2015Review
- Chondroprotective Effect of Kartogenin on CD44-Mediated Functions in Articular Cartilage and Chondrocytes.Cartilage · 2014Article
- Divergent Temporal Expression of Hyaluronan Metabolizing Enzymes and Receptors with Craniotomy vs. Controlled-Cortical Impact Injury in Rat Brain: A Pilot Study.Frontiers in neurology · 2014Article
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
objectiveSmall hyaluronan (HA) oligosaccharides serve as competitive receptor antagonists to displace HA from the cell surface and induce cell signaling events. In articular chondrocytes, this cell signaling is mediated by the HA receptor CD44 and induces stimulation of genes involved in matrix degradation, such as matrix metalloproteinases (MMPs) as well as matrix repair genes including type II collagen, aggrecan, and HA synthase 2. The objective of this study was to determine changes in the expression and function of aggrecanases after disruption of chondrocyte CD44-HA interactions.
methodsBovine articular chondrocytes or bovine cartilage tissue was pretreated with a variety of inhibitors of major signaling pathways prior to the addition of HA oligosaccharides. Changes in aggrecanase were monitored by real-time reverse transcription-polymerase chain reaction and Western blot analyses of ADAMTS-4, ADAMTS-5, and aggrecan proteolytic fragments. To test the interactions between ADAMTS-4 and membrane type 4 MMP (MT4-MMP), protein lysates purified from stimulated chondrocytes were subjected to coimmunoprecipitation.
resultsDisruption of chondrocyte CD44-HA interactions with HA oligosaccharides induced the transcription of ADAMTS-4 and ADAMTS-5 in a time- and dose-dependent manner. The association of glycosyl phosphatidylinositol-anchored MT4-MMP with ADAMTS-4 was also induced in articular chondrocytes by HA oligosaccharides. Inhibition of the NF-κB pathway blocked HA oligosaccharide-mediated stimulation of aggrecanases.
conclusionDisruptive changes in chondrocyte-matrix interactions by HA oligosaccharides induce matrix degradation and elevate aggrecanases via the activation of the NF-κB signaling pathway.
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Registered trials
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