Connectivity Map-Based Discovery of Parbendazole Reveals Targetable Human Osteogenic Pathway
Connectivity Map-based discovery of parbendazole reveals targetable human osteogenic pathway Andrea M. Bruma, Jeroen van de Peppela, Cindy S. van der Leijea, Marijke Schreuders-Koedama, Marco Eijkenb, Bram C. J. van der Eerdena, and Johannes P. T. M. van Leeuwena,1 aDepartment of Internal Medicine, Erasmus MC, 3015 CN Rotterdam, The Netherlands; and bArcarios BV, 3015 CN Rotterdam, The Netherlands Edited by John T. Potts, Massachusetts General Hospital, Charlestown, MA, and approved September 4, 2015 (received for review January 26, 2015) Osteoporosis is a common skeletal disorder characterized by low molecules to a user’s selected gene signature of the phenotype bone mass leading to increased bone fragility and fracture suscepti- of interest using a pattern-matching algorithm with a high level bility. In this study, we have identified pathways that stimulate of resolution and specificity. The screening results in a list of differentiation of bone forming osteoblasts from human mesenchy- compounds with a highly correlating gene expression pattern to mal stromal cells (hMSCs). Gene expression profiling was performed that of the phenotype of interest, which has the potential to aid in hMSCs differentiated toward osteoblasts (at 6 h). Significantly in finding a novel treatment for a disease or to identify novel regulated genes were analyzed in silico, and the Connectivity Map pathways or genes involved in a complex biological process. To (CMap) was used to identify candidate bone stimulatory com- date, the CMap has been successfully used to identify compounds pounds. The signature of parbendazole matches the expression and combination therapies that show promise in the treatment of changes observed for osteogenic hMSCs.
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