No abstract

Since 3D printed hard materials could match the shape of bone, cell survival and fate determination towards osteoblasts in such materials have become a popular research target. In this study, a scaffold of hard material for 3D fabrication was designed to regulate developmental signal (Notch) transduction guiding osteoblast differentiation. We established a polycaprolactone (PCL) and cell-integrated 3D printing system (PCI3D) to reciprocally print the beams of PCL and cell-laden hydrogel for a module. This PCI3D module holds good cell viability of over 87%, whereas cells show about sixfold proliferation in a 7-day culture. The osteocytic MLO-Y4 was engineered to overexpress Notch ligand Dll4, making up 25% after mixing B Xiaolin Tu

Bone formation is critically needed in orthopedic clinical practice. We found that, bone morphogenetic protein-7 (BMP-7) gene expression was significantly increased in fractured mice, which activates canonical Wnt signaling exclusively in osteocytes. Wnt and BMP signaling appear to exhibit synergistic or antagonistic effects in different kinds of cells. However, the communication between Wnt/β-catenin signaling and BMP signaling in osteocytes is almost unknown. Our study verified in vitro that BMP-7 expression was significantly increased when Wnt signaling was activated in osteocytes. Next, BMP-7 in osteocytes was overexpressed using an adenovirus, the osteogenesis of bone marrow stem cells (BMSCs) was enhanced, when cocultured with osteocytes. On the contrary, BMP-7 in osteocytes was silenced using an adenovirus, the osteogenesis of bone marrow stem cells (BMSCs) was weakened. In addition, the osteogenesis of BMSCs was no longer promoted by Wnt-activated osteocytes when BMP-7 was silenced. Therefore, the results showed that BMP-7 mediated the anabolic actions of Wnt/β-catenin signaling in osteocytes. Our study provides new evidence for the clinical application of BMP-7-overexpressed osteocytes.