title: The effects of COX-2 inhibitor during osteogenic differentiation of bone marrow-derived human mesenchymal stem cells.
abstract: 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.
authors.affiliation: Department of Orthopaedic Surgery, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Dong Suk
authors.initials: DS
authors.lastname: Yoon
authors.forename: Je Hyun
authors.initials: JH
authors.lastname: Yoo
authors.forename: Yun Hee
authors.initials: YH
authors.lastname: Kim
authors.forename: Seungil
authors.initials: S
authors.lastname: Paik
authors.forename: Chang Dong
authors.initials: CD
authors.lastname: Han
authors.forename: Jin Woo
authors.initials: JW
authors.lastname: Lee
mesh_terms: 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
chemical_list: 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