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A 3D System for Culturing Human Articular Chondrocytes in Synovial Fluid
Published on: January 31, 2012
The Effects of Naproxen on Chondrogenesis of Human Mesenchymal Stem Cells
John Antoniou1,2, Hong Tian Wang1, Insaf Hadjab1,3
11 Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University , Montreal, Quebec, Canada .
Abstract:
Currently, there are no established treatments to prevent, stop, or even retard the degeneration of articular cartilage in osteoarthritis (OA). Biological repair of the degenerating articular cartilage would be preferable to surgery. There is no benign site where autologous chondrocytes can be harvested and used as a cell source for cartilage repair, leaving mesenchymal stem cells (MSCs) as an attractive option. However, MSCs from OA patients have been shown to constitutively express collagen type X (COL-X), a marker of late-stage chondrocyte hypertrophy. We recently found that naproxen (Npx), but not other nonsteroidal anti-inflammatory drugs, can induce collagen type X alpha 1 (COL10A1) gene expression in bone marrow-derived MSCs from healthy and OA donors. In this study, we determined the effect of Npx on COL10A1 expression and investigated the intracellular signaling pathways that mediate such effect in normal human MSCs during chondrogenesis. MSCs were cultured in standard chondrogenic differentiation media supplemented with or without Npx. Our results show that Npx can regulate chondrogenic differentiation by affecting the gene expression of both Indian hedgehog and parathyroid hormone/parathyroid hormone-related protein signaling pathways in a time-dependent manner, suggesting a complex interaction of different signaling pathways during the process.
Insights
Naproxen (Npx) affects collagen type X gene expression in mesenchymal stem cells (MSCs) during cartilage development. This study explores Npx
Area of Science:
- Biomedical Engineering
- Regenerative Medicine
- Osteoarthritis Research
Background:
- Osteoarthritis (OA) lacks treatments to halt articular cartilage degeneration.
- Mesenchymal stem cells (MSCs) are a promising alternative to autologous chondrocytes for cartilage repair.
- MSCs from OA patients may exhibit undesirable chondrocyte hypertrophy markers.
Purpose of the Study:
- To investigate the effect of naproxen (Npx) on collagen type X alpha 1 (COL10A1) gene expression in human MSCs during chondrogenesis.
- To elucidate the intracellular signaling pathways mediating Npx's effect on COL10A1 expression.
- To understand Npx's role in regulating chondrogenic differentiation for potential OA therapeutic strategies.
Main Methods:
- Human bone marrow-derived MSCs were cultured in chondrogenic differentiation media.
- Cultures were supplemented with or without naproxen (Npx).
- Gene expression of COL10A1, Indian hedgehog, and parathyroid hormone/parathyroid hormone-related protein signaling pathways were analyzed.
Main Results:
- Naproxen (Npx) was found to influence COL10A1 gene expression in MSCs.
- Npx demonstrated a time-dependent effect on the gene expression of Indian hedgehog and parathyroid hormone/parathyroid hormone-related protein signaling pathways.
- These findings suggest a complex interplay of signaling pathways regulated by Npx during chondrogenesis.
Conclusions:
- Naproxen (Npx) can modulate chondrogenic differentiation in human MSCs.
- The drug's effects involve intricate regulation of key signaling pathways, including Indian hedgehog and PTHrP.
- Further research into Npx's mechanism could offer novel therapeutic avenues for osteoarthritis and cartilage repair.

