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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.
AuthorsJohn Antoniou, Hong Tian Wang, Insaf Hadjab, Sultan Aldebeyan, Motaz A Alaqeel, Björn P Meij, Marianna A Tryfonidou, Fackson Mwale
JournalTissue engineering. Part A (Tissue Eng Part A) Vol. 21 Issue 13-14 Pg. 2136-46 (Jul 2015) ISSN: 1937-335X [Electronic] United States
PMID25873236 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Glycosaminoglycans
  • Naproxen
  • Alkaline Phosphatase
Topics
  • Adult
  • Alkaline Phosphatase (metabolism)
  • Cell Differentiation (drug effects)
  • Cells, Cultured
  • Chondrogenesis (drug effects)
  • Gene Expression Regulation (drug effects)
  • Glycosaminoglycans (metabolism)
  • Humans
  • Mesenchymal Stem Cells (cytology, drug effects, enzymology)
  • Naproxen (pharmacology)
  • Young Adult

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