An activator of the cAMP/PKA/CREB pathway promotes osteogenesis from human mesenchymal stem cells
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- An activator of the cAMP/PKA/CREB pathway promotes osteogenesis from human mesenchymal stem cells
- Kim, Jung-Min; Choi, Jin Seok; Kim, Yun-Hee; Jin, Seong Hui; Lim, Seyoung; Jang, Hyun-Jun; Kim, Kyong-Tai; Ryu, Sung Ho; Suh, Pann-Ghill
- PROTEIN-KINASE-A; BONE-MASS; PARATHYROID-HORMONE; LEPTIN SECRETION; OVARIECTOMIZED MICE; GENE-TRANSCRIPTION; SIGNALING PATHWAY; INTERMITTENT PTH; IN-VITRO; OSTEOPOROSIS
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- JOURNAL OF CELLULAR PHYSIOLOGY, v.228, no.3, pp.617 - 626
- 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 pyrazolepyridine, 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.
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