Ap-213 regulates cranial osteogenic potential via the activation of Wnt/ 13-catenin signaling pathway

The skull is a fundamental bone that protects the development of brain and consists of several bony elements, such as the frontal and parietal bones. Frontal bone exhibited superior in osteogenic potential and regeneration of cranial defects compared to parietal bone. However, how this regional difference is regulated remains largely unknown. In this study, we identified an Ap-213 transcriptional factor with a higher expression in frontal bone, but its molecular function in osteoblasts needs to be elucidated. We found that Ap-213 knockdown in preosteoblasts leads to reduced proliferation, increased cell death and impaired differentiation. Through RNA-seq analysis, we found that Ap-213 influences multiple signaling pathways including the Wnt pathway, and overexpression of Ap-213 showed increased nuclear 13-catenin and its target genes expressions in osteoblasts. Pharmacological activation of Wnt/13-catenin signaling using LiCl treatment cannot rescue the reduced luciferase activities of the 13-catenin/TCF/ LEF reporter in Ap-213 knockdown preosteoblasts. Besides, transient expression of Ap-213 via the lentivirus system could sufficiently rescue the inferior osteogenic potential in parietal osteoblasts, while Ap-213 knockdown in frontal osteoblasts resulted in reduced osteoblast activity, reduced active 13-catenin and target genes expressions. Taken together, our data demonstrated that Ap-213 modulates osteoblast proliferation and differentiation through the regulation of Wnt/13-catenin signaling pathway and plays an important role in regulating regional osteogenic potential in frontal and parietal bone.

Automated summary

This study identified Ap-213 as a transcriptional factor with higher expression in frontal bone compared to parietal bone. It regulates osteoblast proliferation and differentiation through the Wnt/13-catenin signaling pathway. Ap-213 plays an important role in regulating regional osteogenic potential in frontal and parietal bone.