title: An activator of the cAMP/PKA/CREB pathway promotes osteogenesis from human mesenchymal stem cells.
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.
authors.affiliation: School of Nano-Bioscience and Chemical Engineering, Ulsan National Institute of Science and Technology, Ulsan, Republic of Korea.
authors.forename: Jung-Min
authors.initials: JM
authors.lastname: Kim
authors.forename: Jin Seok
authors.initials: JS
authors.lastname: Choi
authors.forename: Yun-Hee
authors.initials: YH
authors.lastname: Kim
authors.forename: Seong Hui
authors.initials: SH
authors.lastname: Jin
authors.forename: Seyoung
authors.initials: S
authors.lastname: Lim
authors.forename: Hyun-Jun
authors.initials: HJ
authors.lastname: Jang
authors.forename: Kyong-Tai
authors.initials: KT
authors.lastname: Kim
authors.forename: Sung Ho
authors.initials: SH
authors.lastname: Ryu
authors.forename: Pann-Ghill
authors.initials: PG
authors.lastname: Suh
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D020738:Leptin / Q000096:biosynthesis; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D010012:Osteogenesis / Q000187:drug effects* / Q000502:physiology; D010024:Osteoporosis / Q000188:drug therapy; D011720:Pyrazoles / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: C578304:CW008; D017362:Cyclic AMP Response Element-Binding Protein; D020738:Leptin; D011720:Pyrazoles; D011725:Pyridines; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases