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.

含硼的介孔生物活性玻璃（B-MBG）支架可以通过在骨缺损修复过程中激活Wnt /β-catenin信号通路来促进成骨作用。尽管如此，在很大程度上尚不清楚涉及分子控制的更多内容。在本研究中，我们确定了称为转录因子7样2（TCF7L2）的Wnt /β-catenin信号传导途径的下游是通过硼钙蛋白2（LCN2）促进硼诱导的骨再生和成骨的关键效应器。当用B-MBG支架提取物处理时，TCF7L2在成骨细胞中的表达高于MBG。LCN2作为一种分泌性骨因子，可积极影响MC3T3-E1的成骨分化和体内成骨，这可能是由TCF7L2诱导的。另外，TCF7L2的干扰降低了成骨细胞的成骨分化。最后，我们确定rLCN2可以挽救MC3T3-E1的成骨分化能力差，MC3T3-E1的Tcf7l2基因被慢病毒转染shRNA击倒。我们的发现为硼相关骨再生的分子控制和骨缺损的潜在治疗靶标提供了一些新见解。