title: Effect of acetaminophen and nonsteroidal anti-inflammatory drugs on gene expression of mesenchymal stem cells.
abstract: We have previously shown that mesenchymal stem cells (MSCs) from patients with osteoarthritis (OA) constitutively express type X collagen, a marker of late-stage chondrocyte hypertrophy, osteogenic marker genes, including alkaline phosphatase (ALP), bone sialoprotein (BSP), and osteocalcin (OC), and chondrogenesis marker gene aggrecan (ACAN). As patients with arthritis often take nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen (Acet), the purpose of the study was to assess whether these drugs can affect the gene expression of human MSCs. MSCs isolated from the bone marrow of patients with OA or normal donors were cultured without (control) or with Acet or NSAIDs, which include ibuprofen, diclofenac (Dic), naproxen, and celebrex. After 3 days of culture, the expression of type X collagen alpha 1 (COL10A1), ACAN, COL1A1, as well as ALP, BSP, OC, and Runt-related transcription factor 2 was analyzed by real-time reverse transcription (RT)-polymerase chain reaction. The results showed that COL10A1 and the osteogenic and chondrogenic marker genes can be regulated by NSAIDs and Acet in normal MSCs. In contrast, Acet did not significantly affect COL10A1 expression in OA MSCs, while Dic is the only drug that had no significant effect on all markers in normal MSCs. The upregulation of COL10A1 in normal MCSs by Acet and Npx may explain why stem cells from patients with OA express COL10A1 constitutively. This knowledge may help in designing better strategies for stem cell differentiation into chondrocyte-like cells, from this source, with Dic being a viable option for treating OA pain, with an eye toward preventing the potential to enhance calcification in the repair of cartilage and degenerated intervertebral discs.
authors.affiliation: Orthopaedic Research Laboratory, Division of Orthopaedic Surgery, McGill University and Lady Davis Institute for Medical Research, Montreal, Quebec, Canada.
authors.forename: Abdulaziz
authors.initials: A
authors.lastname: Almaawi
authors.forename: Hong Tian
authors.initials: HT
authors.lastname: Wang
authors.forename: Ovidiu
authors.initials: O
authors.lastname: Ciobanu
authors.forename: Sora A L
authors.initials: SA
authors.lastname: Rowas
authors.forename: Sonia
authors.initials: S
authors.lastname: Rampersad
authors.forename: John
authors.initials: J
authors.lastname: Antoniou
authors.forename: Fackson
authors.initials: F
authors.lastname: Mwale
mesh_terms: D000082:Acetaminophen / Q000494:pharmacology*; D000368:Aged; D000369:Aged, 80 and over; D053674:Aggrecans / Q000235:genetics / Q000378:metabolism; D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D015415:Biomarkers / Q000378:metabolism; D002478:Cells, Cultured; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D024121:Collagen Type X / Q000378:metabolism; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D058574:Integrin-Binding Sialoprotein / Q000235:genetics / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008875:Middle Aged; D010003:Osteoarthritis / Q000235:genetics / Q000473:pathology; D015675:Osteocalcin / Q000235:genetics / Q000378:metabolism
chemical_list: D053674:Aggrecans; D000894:Anti-Inflammatory Agents, Non-Steroidal; D015415:Biomarkers; D024042:Collagen Type I; D024121:Collagen Type X; D050659:Core Binding Factor Alpha 1 Subunit; D058574:Integrin-Binding Sialoprotein; C493709:RUNX2 protein, human; D015675:Osteocalcin; D000082:Acetaminophen; D000469:Alkaline Phosphatase