Uses
production and maintenance of extracellular matrix, cartilage, collagen, differentiation and de-differentiation, signal transduction, apoptosis, differentiation, drug screening, gene expression, cytokine production, agarose assays, chondrocyte adhesion to medical implants, scaffolds for cartilage regeneration
General Description
Human Chondrocytes, HC, are derived from normal human articular cartilage where they produce and maintain the extracellular matrix of cartilage, including type II collagen. Chondrocytes grown in monolayer culture on a solid surface tend to lose their phenotypic markers and became de-differentiated to a fibroblast-like phenotype. This de-differentiation stage can be reversed by culturing them in a semi-solid gel.
Normal Chondrocytes have been adapted as an in vitro model system in multiple studies looking for cellular mechanisms, such as inflammation-related signaling cascades, abnormal proteinase production, chondrocyte apoptosis and differentiation, as well as novel potential treatments for arthritic disease.
Characterization: Positive for aggrecan after differentiation.
Normal Human Chondrocytes (HC) have been used to:
- Develop a high throughput assay to screen for genes capable of inducing an OA-like phenotype in chondrocytes in order to identify key pathways implicated in the disease (Daouti, 2005)
- Elucidate the signaling cascade leading to induction of proinflammatory cytokines by chondrocytes in RA joints (Aida, 2006; Wang, 2011a,b) and effects of elevated IL-6 signaling on normal chondrocytes (Namba, 2007)
- Investigate mechanisms and identify inhibitors of increased production of proteinases by chondrocytes stimulated by interleukin-1 (Aida, 2005; Wada, 2006), retinoic acid (Hikichi, 2009), proinflammatory cytokines (Tanigawa, 2011a,b), nitric oxide (Wu, 2007; Yang, 2011) and shear stress (Wang, 2011b, 2012)
- Investigate the causes of metalloproteinases induction in patients with Lyme disease-associated arthritis (Lin, 2001; Behera, 2004, 2005)
- Study the factors affecting chondrocyte apoptosis (Cherng, 2008; Malemud, 2012) and differentiation into osteoclasts (Watanabe, 2009a,b; Honda, 2011)
- Show that hyaluronate (HA) can prevent the aggravated cartilage degradation by blocking the matrix metalloproteinases production from cytokine-activated chondrocytes via MKP-1 induction through CD44 signaling (Hashizume, 2009, 2010)
- Demonstrate cytotoxic effects of anti-human Fas/APO-1/CD95 (Fas) monoclonal antibody ARG098 on RA synoviocytes and infiltrating lymphocytes, but not on normal chondrocytes (Tamburstuen, 2010)
Normal Chondrocytes were also utilized in a functional cluster formation agarose assay that allows chondrocytes to maintain their differentiated state (Quintavalla, 2005) and to investigate integrin-mediated mechanotransduction pathways required for proper chondrocyte function (Whitney, 2012). Additionally, they have used extensively in material studies aimed to improve chondrocyte adhesion to medical implants (Gutwein, 2002; Ellison, 2003; Price, 2004; Savaiano, 2004; Burns, 2009) and scaffolds for cartilage regeneration (Jun, 2002; Kay, 2002; Miller, 2002a,b; Price, 2002, 2003; Rao, 2004; Park, 2005; Khang, 2008). Normal chondrocyte RNA was used as a gold standard control in research on cellular reprogramming into chondrocytes (Ishii, 2012).
