An activator of the cAMP/PKA/CREB pathway promotes osteogenesis from human mesenchymal stem cells |
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| Authors: | Jung‐Min Kim Jin Seok Choi Yun‐Hee Kim Seong Hui Jin Seyoung Lim Hyun‐Jun Jang Kyong‐Tai Kim Sung Ho Ryu Pann‐Ghill Suh |
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| Affiliation: | 1. School of Nano‐Bioscience and Chemical Engineering, Ulsan National Institute of Science and Technology, Ulsan, Republic of Korea;2. Division of Molecular and Life Sciences, Pohang University of Science and Technology, Pohang, Republic of Korea;3. Central Research Institute, JW Pharmaceutical, Hwaseong, Republic of Korea;4. National Cancer Center, Goyang, Republic of Korea |
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| 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. |
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