OIC-A006 promotes osteogenesis in vitro and in vivo.
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.
Cai
Ming
M
Shanghai Institute of Traumatology and Orthopedics, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, P.R. of China.
Liu
Xiaodong
X
Shao
Jin
J
Qi
Jin
J
Wang
Jun
J
Zhu
Yaping
Y
Zhou
Qi
Q
Wang
Jinshen
J
Zhao
Qiang
Q
Li
Guosong
G
Liang
Jing
J
Lu
W W
WW
Deng
Lianfu
L
D000469:Alkaline Phosphatase / Q000096:biosynthesis; D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism; D002113:Calcification, Physiologic / Q000187:drug effects; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D007150:Immunohistochemistry; D008682:Metatarsal Bones / Q000187:drug effects / Q000254:growth & development; D051379:Mice; D008810:Mice, Inbred C57BL; D015675:Osteocalcin / Q000096:biosynthesis / Q000235:genetics; D010012:Osteogenesis / Q000187:drug effects*; D053495:Osteopontin / Q000096:biosynthesis / Q000235:genetics; D011247:Pregnancy; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012886:Skull / Q000002:abnormalities / Q000187:drug effects / Q000254:growth & development; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism
D050659:Core Binding Factor Alpha 1 Subunit; D015675:Osteocalcin; D053495:Osteopontin; D000469:Alkaline Phosphatase