Ibuprofen and other Non-Steroidal Antiinflammatory Drugs

EFFECT OF ACETAMINOPHEN AND NONSTEROIDAL ANTI-INFLAMMATORY DRUGS ON GENE EXPRESSION OF MESENCHYMAL STEM CELLS.

"Mesenchymal stem cells (MSCs) from osteoarthritic (OA) patients constitutively express type X collagen (COL X), a marker of late stage chondrocyte hypertrophy, osteogenic marker genes including alkaline phosphatase (ALP), bone sialoprotein (BSP), osteocalcin (OC) and chondrogenesis marker gene aggrecan (ACAN). As arthritis patients often take non-steroidal 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 OA patients or normal donors were cultured without (control) or with Acet or NSAIDs, which include Ibuprofen (Ibu), Diclofenac (Dic), Naproxen (Npx) and Celebrex (Cele). After 3 days of culture, [we] analyze the expression of COL10A1, ACAN, COL1A1, as well as ALP, BSP, OC and Runt-related transcription factor 2 (RUNX2). 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 up-regulation of COL10A1 in normal MCSs by Acet and Npx may explain why stem cells from OA patients express COL10A1 constitutively."

"the concentrations of Npx, Ibu, Dic, Cele, Acet were 100 μg/mL, 300 μg/mL, 5 μg/mL, 800 ng/mL and 50 μg/mL respectively."

"ALP and BSP are prominent in OA MSCs, followed by COL 10A1, ACAN and OC when compared to MSCs from normal donors"

"In normal MSCs, Acet and Npx supplementation led to a significant increase in COL10A1 expression"

"In OA MSCs, only Npx supplementation led to a significant increase in COL10A1 expression"

"In normal MSCs, Cele supplementation led to a significant increase in ALP expression"

"Acet, Ibu and Npx supplementation led to a significant decrease in ALP expression"<-Maybe these supplements can be used to encourage chondrogenic over osteogenic differentiation?

"In OA MSCs, Npx supplementation led to a significant decrease in ALP expression"

"In normal MSCs, Acet supplementation decreased the expression of BSP.  Dic had a tendency to enhance BSP expression." 

"In OA MSCs, Dic supplementation led to a significant decrease in BSP expression."

"In normal MSCs, Acet and Npx supplementation led to a significant increase in OC expression when compared to control"

"In OA MSCs, Acet and Npx supplementation led to a significant increase in OC expression"

"In normal [and OA] MSCs, the addition of Npx led to a significant increase in RUNX2 expression"

"[In OA MSCs], Ibu and Dic supplementation decreased RUNX2 expression"

"After culturing normal and OA MSCs cells for 3 days in the absence of drugs, ACAN expression could be detected in normal MSCs"

"With Acet, Ibu and Npx supplementation, ACAN message levels were decreased"

"Addition of Cele increased ACAN gene expression"

"In OA MSCs, with Acet, Dic and Npx supplementation, ACAN message levels were decreased significantly [while] Cele increased ACAN expression significantly"

"In normal MSCs, in the presence of Acet, Ibu and Npx, significant decreased COL1A1 message levels were observed while Cele significantly increased COL1A1 expression"  COL1A1 was present in normal MSCs without drugs.

"COL I but not COL II was detected in MSCs from OA patients"

"All NSAIDs can be found in Synovial fluid after repeated dosing"

"Ibu, Npx and Dic are non-selective COX inhibitors. Cele is a selective COX-2 inhibitor and has about 375 times more selectivity for COX-2 than for COX-1. Acet is a weak inhibitor of COX activity with weak anti-inflammatory activity."

I think based on this study Celebrex and Acetaminophen look the most promising to promote chondrogenesis but neither drug favors chondrogenic over osteogenic proteins uniformly.