Indomethacin is used in prevention of heterotopic ossification (HO) and as postoperative pain therapy. By perioperative administration of cyclooxygenase inhibitors, a significant reduction of HO after hip replacement surgery could be observed in different clinical surveys. In contrast there is indication for the stable prostacyclin analogon iloprost to have regenerative curative potential in treatment of bone marrow edema and avascular osteonecrosis. In this study the influence of indomethacin and iloprost on proliferation and differentiation of mesenchymal stroma cells (MSCs) from human bone marrow into osteoblast was investigated in vitro.Bone marrow cells of eight donors were isolated by density gradient centrifugation, expanded, examined for mesenchymal surface antigene (CD73+CD105+CD14-CD45-) by flow cytometry and cultivated for 28 days without dexamethason-ascorbic acid-beta glycerolphosphate (DAG) as follows: Without indomethacin as control, with administration of 10−7 M iloprost, with 10−6, 10−5, 10−4 M indomethacin with and without 10−7 M iloprost. On day 10 and 28, UV/Vis spectrometric and immunocytochemical assays and reverse trancriptase polymerase chain reaction (RT-PCR) were performed to investigate cell proliferation and differentiation towards the osteoblastic lineage (Runx2, type 1 collagen (Col1), osteocalcin (OC), alkaline phosphatase (ALP), Twist, specific ALP-activity).It could be demonstrated that a combination of indomethacin and iloprost suppressed twist expression—an effect that has not been mentioned before. Further indomethacin suppressed the osteoblastic markers Col1, Runx2 and OC in immunocytochemistry. Iloprost alone supported the expression of Runx2 and increased specific ALP activity on day 28 and proliferation in some donors, whereas results with administration of indomethacin varied donor-dependently.Iloprost seems to have osteoblast protective potential. In the treatment of avascular osteonecrosis or painful bone marrow edema the undesirable effects of indomethacin might be counterbalanced by iloprost.
|Advisor:||Jäger , Marcus|
|School:||Universitaet Duisburg-Essen (Germany)|
|Source:||DAI-C 81/1(E), Dissertation Abstracts International|
|Keywords:||Indomethacin, Iloprost, Mesenchymal progenitor cells|
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