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An activator of the cAMP/PKA/CREB pathway promotes osteogenesis from human mesenchymal stem cells
Author(s) -
Kim JungMin,
Choi Jin Seok,
Kim YunHee,
Jin Seong Hui,
Lim Seyoung,
Jang HyunJun,
Kim KyongTai,
Ryu Sung Ho,
Suh PannGhill
Publication year - 2013
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.24171
Subject(s) - mesenchymal stem cell , creb , osteoblast , microbiology and biotechnology , teriparatide , cellular differentiation , regenerative medicine , activator (genetics) , chemistry , stem cell , biology , endocrinology , osteoporosis , transcription factor , receptor , bone mineral , in vitro , biochemistry , gene
Abstract Mesenchymal stem cells (MSCs) are multipotent adult stem cells capable of differentiating along the osteoblast, adipocyte, and chondrocyte lineages. Regulation of MSCs differentiation may be a useful tool for regenerative medicine and cell‐based therapy. The discovery of small molecule that activates the osteogenic differentiation of MSCs could aid in the development of a new anabolic drug for osteoporosis treatment. We identified CW008, a derivative of pyrazole–pyridine, that stimulates osteoblast differentiation of human MSCs and increases bone formation in ovariectomized mice. CW008 promotes osteogenesis by activating cAMP/PKA/CREB signaling pathway and inhibiting leptin secretion. These results suggest that CW008 is an agonist of cAMP/PKA/CREB pathway in osteogenic differentiation and that application of CW008 may be useful for the treatment of bone‐related diseases and for the study of bone biology. J. Cell. Physiol. 228: 617–626, 2013. © 2012 Wiley Periodicals, Inc.