Role of sodium potassium pump in osteoinduction process of calcium phosphate ceramic

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Event Abstract Back to Event Role of sodium potassium pump in osteoinduction process of calcium phosphate ceramic Zhurong Tang1, Pengfei Xie1, Xiangdong Zhu1, Yujiang Fan1, Xingdong Zhang1 and Xiao Yang1 1 Sichuan University, National Engineering Research Center for Biomaterials, China Sodium potassium pump (Na+-K+ ATPase, NKA) is essential in regulation of intracellular calcium concentration. In a gene array study, Bone morphogenetic protein 2 (BMP2) was found to cause a 3-fold increment in gene expression of NKA subunit in human marrow stromal cells[1]. Thus, we hypothesized that the activation of NKA might be essential in bone forming process induced by calcium phosphate ceramics too. In vivo and in vitro experiments involving osteoinductive BCP bulk material (HA: beta-TCP = 2:8) with addition of several NKA inhibitor and activator agents were conducted. When co-cultured with BCP material, elevated gene expression of NKA alpha 1 and beta 4 subunits in mesenchymal stem cells (MSCs) were discovered. Furthermore, BMP2, OSX and BSP gene expressions in MSCs was significantly higher in the BCP material co-culture group than the cell alone control group. Adding in NKA specific inhibitors (ouabain or digoxin) in the BCP co-culture system will largely decrease the expression of BMP2 gene, whilst adding in NKA specific activator (SSA412) will increased BMP2 expression. Cell proliferation was not affected by any of these agents. Intramuscular implantation mouse model was used to evaluate ectopic bone formation induced by BCP alone and with exposure to NKA activator and inhibitors. Cylindrical BCP samples were immersed in ouabain, digoxin, SSA412 and vehicle solution before surgery. During the surgery, the BCP samples were implanted into the bilateral muscle pouches of each animal. The implants were retrieved after 3 month. The incidence of bone formation and bone area was significantly higher in SSA412 + BCP group. No pathological change was found in organs harvested. We conclude that the activity of NKA played an important in osteoinduction process. The authors wish to acknowledge the financial support from the National Science and Technology Supporting Project, Grant No. 2012BAI17B01; National Basic Research Program of China (973 project), Grant No. 2011CB606201.