The effects of COX-2 inhibitor during osteogenic differentiation of bone marrow-derived human mesenchymal stem cells.
Cyclooxygenase-2 (COX-2) inhibitors suppress bone repair and bone formation by suppressing angiogenesis as well as potentially interfering with osteoblast and osteoclast functions. In spite of these reports, there is a controversy over the exact effects of COX-2 inhibitors on bone formation processes itself. This work was designed to investigate the effect of COX-2 inhibitor on osteogenesis of human bone marrow-derived mesenchymal stem cells (MSC). MSCs in osteogenesis were treated with COX-2 inhibitor (celecoxib and naproxen) in the absence or presence of interleukin-1β (IL-1β), which was used to induce inflammation. Following differentiation, alkaline phosphatase (ALP) and calcium contents of IL-1β-treated MSC were significantly reduced by high doses of COX-2 inhibitors compared with the low-dose group. However, in non-inflammatory-conditioned MSCs, ALP and calcium contents were not reduced by COX-2 inhibitors. The mRNA expression of Runx2/Cbf alpha 1, Dlx5, and osteocalcin was also decreased by COX-2 inhibitors in inflammatory-conditioned MSCs and showed a significant decrease for the high dose while they remained constant in the non-inflammatory-conditioned MSCs. These data indicate that the osteogenic potential of MSC is inhibited/delayed by the treatment of high-dose NSAIDs under inflammatory conditions.
Yoon
Dong Suk
DS
Department of Orthopaedic Surgery, Yonsei University College of Medicine, Seoul, South Korea.
Yoo
Je Hyun
JH
Kim
Yun Hee
YH
Paik
Seungil
S
Han
Chang Dong
CD
Lee
Jin Woo
JW
D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use; D015415:Biomarkers / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000502:physiology*; D000068579:Celecoxib; D002454:Cell Differentiation / Q000187:drug effects*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000235:genetics; D053583:Interleukin-1beta / Q000494:pharmacology; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D008875:Middle Aged; D009288:Naproxen / Q000494:pharmacology; D010012:Osteogenesis / Q000187:drug effects*; D011720:Pyrazoles / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology; D055815:Young Adult
D000894:Anti-Inflammatory Agents, Non-Steroidal; D015415:Biomarkers; D052246:Cyclooxygenase 2 Inhibitors; D053583:Interleukin-1beta; D011720:Pyrazoles; D012333:RNA, Messenger; D013449:Sulfonamides; D009288:Naproxen; D051546:Cyclooxygenase 2; D000068579:Celecoxib