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OIC-A006 promotes osteogenesis in vitro and in vivo
Authors:Cai Ming  Liu Xiaodong  Shao Jin  Qi Jin  Wang Jun  Zhu Yaping  Zhou Qi  Wang Jinshen  Zhao Qiang  Li Guosong  Liang Jing  Lu W W  Deng Lianfu
Affiliation:Shanghai Institute of Traumatology and Orthopedics, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, P.R. of China.
Abstract:Bone morphogenesis proteins (BMPs) are one of the potent bone-forming factors. However, the safety, utility, and cost effectiveness of BMPs must be considered. Nowadays, there has been substantial interest in developing a chemical compound that safely promotes bone formation and facilitates fracture repair. Based on previous research with high throughout screening assay, we found one potent osteogenic inductive compound, named as OIC-A006 (Osteogenic inducible compound-active 006), which is classified in the amine family. In this study, we aimed to investigate the inducing effects of OIC-A006 on osteogenesis by bone marrow stem cells (BMSCs) in vitro and in vivo. We demonstrated that OIC-A006, at different concentrations, especially at optimal concentration of 6.25 microM, could stimulate BMSCs to express alkaline phosphatase (ALP), core-binding factor a1 (Cbfa1), osteopontin (OPN) and osteocalcin (OC), and to form calcified nodules in vitro. Under the bone tissue culture conditions, OIC-A006 also stimulated new bone formation of murine calvarial and metatarsal bone, indicating that OIC-A006 may exert positive effects on osteogenesis. Furthermore, to elucidate the in vivo osteogenic potential of OIC-A006, we used a rabbit skull defect model treated with sustained release microcapsules (OIC-A006/PLGA-MC) injected s.c. adjacent to the defect. These results revealed, for the first time, that OIC-A006 has the potential to promote osteogenesis in vitro and in vivo. This new compound may provide a new alterative agent for growth factors to promote bone healing and bone regeneration.
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