Bone morphogenetic protein 2 (BMP-2) has been used clinically to encourage bone regeneration; although, there can be major side effects with larger doses. Therefore, there is a need to identify new small molecules to potentiate the osteogenic action of BMP-2. In this study, we investigated the effect of mollugin on bone formation in murine bi-potential mesenchymal progenitor C2C12 cells by combination with BMP-2. We found mollugin could enhance the BMP-2-mediated osteoblast differentiation of C2C12 cells. This was accompanied by the induction of other osteogenic BMPs. We also found the enhancing potential of mollugin may involve activation of the p38–Smad1/5/8 signaling axis. Furthermore, mollugin promoted skeletal development in zebrafish. The combination of BMP-2 with small molecules, including mollugin, could minimize its clinical limitations, and these molecules might lead to the development of effective stem cell stimulants for bone regeneration and fracture healing.
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Acknowledgements This work was supported by a project Grant (KK1703-F02) from the Korea Research Institute of Chemical Technology.
All Science Journal Classification (ASJC) codes
- Molecular Medicine
- Drug Discovery
- Organic Chemistry