ArticleScientific reports2019
Inhibition of CD44 intracellular domain production suppresses bovine articular chondrocyte de-differentiation induced by excessive mechanical stress loading.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 15 citations in OpenAlex.
- Effect of distraction length on the morphology of knee cartilage in a rat model of femoral distraction osteogenesis.Frontiers in physiology · 2026Article
- Proteomic analysis of hydrogen peroxide-treated human chondrocytes shows endoplasmic reticulum stress, cytoskeleton remodeling, and altered secretome composition.Cell communication and signaling : CCS · 2025Article
- Spatiotemporal Analysis of Mesenchymal Stem Cells Fate Determination by Inflammatory Niche Following Soft Tissue Injury at a Single-Cell Level.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Inhibiting CD44-ICD Attenuates LPS-Induced Initiation of Hepatic Inflammation in Septic Mice.International journal of molecular sciences · 2024Article
- Effects of different combinations of mechanical loading intensity, duration, and frequency on the articular cartilage in mice.Molecular biology reports · 2024Article
- A high throughput cell stretch device for investigating mechanobiologyAPL bioengineering · 2024Article
- Review
- Activation of transient receptor potential vanilloid 4 protects articular cartilage against inflammatory responses via CaMKK/AMPK/NF-κB signaling pathway.Scientific reports · 2021Article
- Proteolytic Processing of CD44 and Its Implications in Cancer.Stem cells international · 2021Review
- Cartilage tissue engineering for obesity-induced osteoarthritis: Physiology, challenges, and future prospects.Journal of orthopaedic translation · 2021Review
- Hyaluronan suppresses enhanced cathepsin K expression via activation of NF-κB with mechanical stress loading in a human chondrocytic HCS-2/8 cells.Scientific reports · 2020Article
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
CD44 fragmentation is enhanced in chondrocytes of osteoarthritis (OA) patients. We hypothesized that mechanical stress-induced enhancement of CD44-intracellular domain (CD44-ICD) production plays an important role in the de-differentiation of chondrocytes and OA. This study aimed to assess the relationship between CD44-ICD and chondrocyte gene expression. Monolayer cultured primary bovine articular chondrocytes (BACs) were subjected to cyclic tensile strain (CTS) loading. ADAM10 inhibitor (GI254023X) and γ-secretase inhibitor (DAPT) were used to inhibit CD44 cleavage. In overexpression experiments, BACs were electroporated with a plasmid encoding CD44-ICD. CTS loading increased the expression of ADAM10 and subsequent CD44 cleavage, while decreasing the expression of SOX9, aggrecan, and type 2 collagen (COL2). Overexpression of CD44-ICD also resulted in decreased expression of these chondrocyte genes. Both GI254023X and DAPT reduced the production of CD44-ICD upon CTS loading, and significantly rescued the reduction of SOX9 expression by CTS loading. Chemical inhibition of CD44-ICD production also rescued aggrecan and COL2 expression following CTS loading. Our findings suggest that CD44-ICD is closely associated with the de-differentiation of chondrocytes. Excessive mechanical stress loading promoted the de-differentiation of BACs by enhancing CD44 cleavage and CD44-ICD production. Suppression of CD44 cleavage has potential as a novel treatment strategy for OA.
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