title: The Effects of Naproxen on Chondrogenesis of Human Mesenchymal Stem Cells.
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.
authors: 1 Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University , Montreal, Quebec, Canada .|2 Division of Orthopedic Surgery, McGill University , Montreal, Quebec, Canada .
authors: John
authors: J
authors: Antoniou
authors: 1 Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University , Montreal, Quebec, Canada .
authors: Hong Tian
authors: HT
authors: Wang
authors: 1 Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University , Montreal, Quebec, Canada .|3 École Polytechnique , Montreal, Quebec, Canada .
authors: Insaf
authors: I
authors: Hadjab
authors: 1 Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University , Montreal, Quebec, Canada .|4 Department of Orthopaedic Surgery, King Fahad Medical City, Riyadh, Saudi Arabia .
authors: Sultan
authors: S
authors: Aldebeyan
authors: 1 Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University , Montreal, Quebec, Canada .|5 Department of Orthopedics, College of Medicine, King Saud University , Riyadh, Saudi Arabia .
authors: Motaz A
authors: MA
authors: Alaqeel
authors: 6 Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University , Utrecht, The Netherlands .
authors: Björn P
authors: BP
authors: Meij
authors: 6 Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University , Utrecht, The Netherlands .
authors: Marianna A
authors: MA
authors: Tryfonidou
authors: 1 Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University , Montreal, Quebec, Canada .|2 Division of Orthopedic Surgery, McGill University , Montreal, Quebec, Canada .
authors: Fackson
authors: F
authors: Mwale
mesh_terms: D000328:Adult; D000469:Alkaline Phosphatase / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D020219:Chondrogenesis / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D006025:Glycosaminoglycans / Q000378:metabolism; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D009288:Naproxen / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D006025:Glycosaminoglycans; D009288:Naproxen; D000469:Alkaline Phosphatase