Healing of osteoporotic bone defects by baculovirus-engineered bone marrow-derived MSCs expressing MicroRNA sponges. (January 2016)

• Record Type: Journal Article
• Authors: Li, Kuei-Chang; Chang, Yu-Han; Yeh, Chia-Lin; Hu, Yu-Chen
• Is Part Of: Biomaterials. Volume 74(2016)
• Page Start: 155
• Page End: 166
• Publication Date: 2016-01
• Subjects: Osteoporosis -- Bone defect -- MicroRNA -- miR-214 -- BMP2 -- miRNA sponge; Biomedical materials -- Periodicals; Biocompatible Materials -- Periodicals; Biomatériaux -- Périodiques; 610.28
• DOI: 10.1016/j.biomaterials.2015.09.046
• Languages: English
• ISSNs: 0142-9612

Abstract

Abstract: Fractures associated with osteoporosis are a worldwide health problem. To augment osteoporotic bone healing, we aimed to develop a cell/gene therapy approach in combination with miRNA manipulation. We unraveled aberrant overexpression of miR-140* and miR-214 in the bone marrow-derived MSCs isolated from ovariectomized (OVX) rats (OVX-BMSCs). To suppress the miRNA levels, we constructed hybrid baculovirus vectors expressing miRNA sponges to antagonize miR-140* or miR-214. Engineering OVX-BMSCs with the hybrid vectors persistently attenuated the cellular miR-140*/miR-214 levels, which promoted the OVX-BMSCs osteogenesis and augmented the ability of OVX-BMSCs to repress osteoclast maturation in vitro . Notably, suppressing miR-214 exerted more potent osteoinductive effects. In the osteoporotic rat models with a critical-size bone defect at the femoral metaphysis, implanting the OVX-BMSCs ectopically expressing BMP2 failed to heal the defect, which underscored the difficulty to heal osteoporotic bone defects. Nonetheless, allotransplantation of the miR-214 sponges-expressing OVX-BMSCs healed the defect and ameliorated the bone quality (density, trabecular number, trabecular thickness and trabecular space) at 4 weeks post-implantation. Co-expressing BMP2 and miR-214 sponges in OVX-BMSCs further synergistically substantiated the healing. The baculovirus-engineered OVX-BMSCs that expressed miR-214 sponge, with or without BMP2 expression, thus paved a new avenue to the treatment of osteoporotic bone defects.