ArticleOsteoarthritis and cartilage2010
Hyaluronan oligosaccharide treatment of chondrocytes stimulates expression of both HAS-2 and MMP-3, but by different signaling pathways.
Article in Osteoarthritis and cartilage, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 20 citations in OpenAlex.
- Mechanisms Underlying the Stimulation of DUSP10/MKP5 Expression in Chondrocytes by High Molecular Weight Hyaluronic Acid.Biomedicines · 2025Article
- Hypoxia as a Stimulus for the Maturation of Meniscal Cells: Highway to Novel Tissue Engineering Strategies?International journal of molecular sciences · 2021Article
- 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 pericellular hyaluronan of articular chondrocytes.Matrix biology : journal of the International Society for Matrix Biology · 2019Review
- Biomimetic molecules lower catabolic expression and prevent chondroitin sulfate degradation in an osteoarthritic ex vivo model.ACS biomaterials science & engineering · 2016Article
- Article
- Functional imaging in OA: role of imaging in the evaluation of tissue biomechanics.Osteoarthritis and cartilage · 2014Review
- CD44 and hyaluronan promote the bone morphogenetic protein 7 signaling response in murine chondrocytes.Arthritis & rheumatology (Hoboken, N.J.) · 2014Article
- Intracellular domain fragment of CD44 alters CD44 function in chondrocytes.The Journal of biological chemistry · 2013Article
- Hyaluronic acid fragments enhance the inflammatory and catabolic response in human intervertebral disc cells through modulation of toll-like receptor 2 signalling pathways.Arthritis research & therapy · 2013Article
- Mechanisms involved in enhancement of the expression and function of aggrecanases by hyaluronan oligosaccharides.Arthritis and rheumatism · 2012Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
objectiveSmall hyaluronan (HA) oligosaccharides 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 includes stimulation of genes involved in matrix degradation such as matrix metalloproteinases (MMPs) as well as matrix repair genes including collagen type II, aggrecan and HA synthase-2 (HAS-2). The objective of this study was to determine whether stimulation of HAS-2 and MMP-3 by HA oligosaccharides is due to the activation of a single, cascading pathway or multiple signaling pathways.
methodBovine articular chondrocytes were pre-treated with a variety of inhibitors of major signaling pathways prior to the addition of HA oligosaccharides. Changes in HA were monitored by real time reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of HAS-2 mRNA, HA ELISA and HA accumulation at the cell surface. A 1900 base pair sequence containing the proximal promoter of HAS-2 was inserted into a luciferase reporter construct, transfected into human immortalized chondrocytes and assayed in a similar fashion.
resultsWhile our previous studies demonstrated that HA oligosaccharides stimulate MMP-13 activity via activation of p38 MAP kinase and NF-kappaB, inhibitors of these pathways did not affect the stimulation of HAS-2 mRNA expression. However, inhibiting the phosphatidylinositol-3-kinase pathway blocked HA oligosaccharide-mediated stimulation of HAS-2 yet had no effect on MMP-3. Wortmannin and LY294002 also blocked HA oligosaccharide-induced serine and threonine Akt phosphorylation. Treatment of transfected immortalized chondrocytes with HA oligosaccharides resulted in stimulation of HAS-2 mRNA, activation of Akt and enhanced luciferase activity-activity that was blocked by inhibitors of Akt phosphorylation.
conclusionsChanges in chondrocyte-matrix interactions by HA oligosaccharides induce altered matrix metabolism by the activation of least two distinct signaling pathways.
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