Novel insights into the mechanism of decreased expression of type X collagen in human mesenchymal stem cells from patients with osteoarthritis cultured on nitrogen-rich plasma polymers: implication of cyclooxygenase-1.
Recent evidence indicates that a major drawback of current cartilage- and intervertebral disc (IVD) tissue engineering is that human mesenchymal stem cells (MSCs) from patients with osteoarthritis rapidly express type X collagen (COL10A1), a marker of late stage chondrocyte hypertrophy associated with endochondral ossification. We recently demonstrated that COL10A1 expression was inhibited in MSCs from patients with osteoarthritis cultured on nitrogen-rich plasma polymerized (PPE:N) coatings. Here, we sought to understand the mechanisms of action of this effect by culturing MSCs on PPE:N surfaces in the presence of different inhibitors of kinases and cyclooxygenases. The effect of PPE:N surfaces on COL10A1 expression was found to be mimicked by the cyclooxygenase inhibitor NPPB, but not by daphnetin (an inhibitor of protein kinases) nor by genistein (an inhibitor of tyrosine kinases). COL10A1 expression was also suppressed by the specific cyclooxygenase-1 (COX-1: SC-560) and 5-lipoxygenase (5-LOX: MK-866) inhibitors, but not by COX-2 (COX-2 inhibitor 2) and 12-LOX (baicalein) inhibitors. Finally, the incubation of MSCs on PPE:N surfaces inhibited the expression of COX-1 while 5-LOX was not expressed in these cells. Taken together, these results indicate that PPE:N surfaces inhibit COL10A1 expression via the suppression of COX-1.
Lady Davis Institute for Medical Research, SMBD-Jewish General Hospital, Montreal, Quebec, Canada.
Alain
A
Petit
Hong Tian
HT
Wang
Pierre-Luc
PL
Girard-Lauriault
Michael R
MR
Wertheimer
John
J
Antoniou
Fackson
F
Mwale
D000368:Aged; D000369:Aged, 80 and over; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism; D001672:Biocompatible Materials / Q000737:chemistry / Q000378:metabolism; D002478:Cells, Cultured; D020099:Coated Materials, Biocompatible; D024121:Collagen Type X / Q000378:metabolism*; D051545:Cyclooxygenase 1 / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000378:metabolism; D006801:Humans; D008422:Materials Testing; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology*; D008875:Middle Aged; D009584:Nitrogen / Q000737:chemistry* / Q000378:metabolism; D010003:Osteoarthritis / Q000378:metabolism* / Q000473:pathology; D011108:Polymers / Q000737:chemistry / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D023822:Tissue Engineering / Q000379:methods
D001672:Biocompatible Materials; D020099:Coated Materials, Biocompatible; D024121:Collagen Type X; D004791:Enzyme Inhibitors; D011108:Polymers; D012313:RNA; D001094:Arachidonate 5-Lipoxygenase; D051545:Cyclooxygenase 1; D009584:Nitrogen