TCF7L2 Promotes Osteogenic Differentiation and Boron-Induced Bone Repair Via Lipocalin 2

Abstract

Boron-containing mesoporous bioactive glass (B-MBG) scaffolds are capable of promoting osteogenesis during the process of bone defect repair. Despite this, the involving molecular controls are still largely unclear. We identified that transcription factor 7-like 2 (TCF7L2) served as a key effector promoting boron-induced bone regeneration through lipocalin 2. Lipocalin 2 was highly expressed in osteoblasts treated with B-MBG scaffolds extraction than MBG, as well as TCF7L2. Lipocalin 2, as a secreted bone factor, positively affected osteogenic differentiation of MC3T3-E1 and osteogenesis in vivo, which can be induced by TCF7L2. In addition, interference of TCF7L2 decreased the osteogenic differentiation of MC3T3-E1 in vitro, as well as bone mass, and width growth plate in Ubc-Cre;Tcf7l2^fl/fl mice. Finally, we identified lipocalin-2 as a pivotal factor that can rescue the poor ability of osteogenic differentiation of MC3T3-E1 in which TCF7L2 gene was knocked down by lentiviral transfection of shRNA. Our findings provide some new insights into the molecular controls of boron-associated bone regeneration and potential therapeutic targets for the treatment of bone defects.