Transcription factor 7-like 2 promotes osteogenic differentiation and boron-induced bone repair via lipocalin 2

Abstract

Boron-containing mesoporous bioactive glass (B-MBG) scaffolds could be capable of promoting osteogenesis by activating Wnt/β-catenin signaling pathway during the process of bone defect repair. Despite this, more involving molecular controls are still largely unclear. In the present study, we identified that the downstream of Wnt/β-catenin signaling pathway named transcription factor 7-like 2 (TCF7L2) served as a key effector to promote boron-induced bone regeneration and osteogenesis through lipocalin 2 (LCN2). TCF7L2 was highly expressed in osteoblasts when treated with B-MBG scaffold extraction than MBG. LCN2, as a secreted bone factor, positively affected osteogenic differentiation of MC3T3-E1 and osteogenesis in vivo, which could be induced by TCF7L2. In addition, interference of TCF7L2 decreased the osteogenic differentiation of osteoblasts. Finally, we identified that rLCN2 could rescue the poor ability of osteogenic differentiation of MC3T3-E1 whose 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.

Keywords: Bone regeneration; Boron; Lipocalin 2; Osteogenesis; Transcription factor 7-like 2.